Auswahl der wissenschaftlichen Literatur zum Thema „Side-chain effect“

Thesis (Ph.D.)--University of Cincinnati, 2009.
Advisors: H. Brian Halsall PhD (Committee Chair), William Heineman PhD (Committee Co-Chair), Patrick Limbach PhD (Committee Member), Pearl Tsang PhD (Committee Member). Title from electronic thesis title page (viewed July 25, 2009). Keywords: Chlorine; hypochlorous acid; immunoassay; tryptophan; indole acetic acid; paramagnetic microbead. Includes abstract. Includes bibliographical references.

Side chains in protein crystal structures are essential for understanding biochemical processes such as catalysis and molecular recognition. However, crystal packing could influence side-chain conformation and dynamics, thus complicating functional interpretations of available experimental structures. Here we investigate the effect of crystal packing on side-chain conformational dynamics with crystal and solution molecular dynamics simulations using Cyanovirin-N as a model system. Side-chain ensembles for solvent-exposed residues obtained from simulation largely reflect the conformations observed in the X-ray structure. This agreement is most striking for crystal-contacting residues during crystal simulation. Given the high level of correspondence between our simulations and the X-ray data, we compare side-chain ensembles in solution and crystal simulations. We observe large decreases in conformational entropy in the crystal for several long, polar and contacting residues on the protein surface. Such cases agree well with the average loss in conformational entropy per residue upon protein folding and are accompanied by a change in side-chain conformation. This finding supports the application of surface engineering to facilitate crystallization. Our simulation-based approach demonstrated here with Cyanovirin-N establishes a framework for quantitatively comparing side-chain ensembles in solution and in the crystal across a larger set of proteins to elucidate the effect of the crystal environment on protein conformations.

By flavin's unique structure, nature predestined riboflavin and its derivatives to the participation in redox processes within the bodies of all the living organisms. These biomolecules draw attention with intriguing optical properties and photosensitising abilities. Nature-inspired flavin derivatives share these qualities, and there is also a possibility of fine-tuning for the particular application from the chemical point of view. The thesis deals with two main aims. The first aim handles the synthesis of the trimer heteroaromatic precursor and 1,2-diketone. These key intermediates are essential for the future synthesis of the central aromatic core of the novel NH-free non-fused flavin derivative. The thesis introduces and verifies three approaches, including oxidation of diarylalkynes, nucleophilic addition of a corresponding organolithium compound to a Weinreb amide and benzoin condensation. The second aim covers the properties customization of NH-free fused systems by implementation of linear and bulky alkyl side-chains on the nitrogen atoms N1 and N3 of the alloxazine dilactam. N,N-alkylation introduced an increase in solubility in common organic solvents dichloromethane and chloroform. For the derivatives with 2-(adamantan-1-yl)ethyl substituents, high thermal stability was observed via TGA.

Anthocyanins are plant pigments offering a range of colours to fruits and flowers. Many properties of anthocyanins are influenced by the degree and type of side chain modifications. Though much is known about the biosynthesis of anthocyanins and the enzymes involved in side-chain decoration, there is limited understanding of the structural features of anthocyanin acyltransferases that determine their substrate preference. Anthocyanin acyltransferases belong to the BAHD family of enzymes and are involved in acylation. Through mutagenesis I showed that an arginine positioned close to motif-1 in aliphatic anthocyanin acyltransferase determines the enzyme’s specificity for malonyl transfer. Modification of arginine to phenylalanine in Ch3MAT, led to gain of acetylation property. This study thus suggests that CoA interacting residues are conserved in aliphatic acyltansferases. A phenylalanine in a similar position, close to motif 1 in aromatic anthocyanin acyltransferases is crucial for the specificity for aromatic-CoA of aromatic acyltransferases. To understand the influence of different side-chain modifications on the formation of anthocyanic vacuolar inclusions (AVIs), I showed that coumaroylation of anthocyanins leads to AVI formation when high levels of anthocyanins are accumulating. Malonylation does not lead to the formation of AVIs, suggesting that the ability of aromatic moieties to form intra-molecular stacks can cause formation of AVIs. Neither the presence of flavonols nor light or high amounts of anthocyanins can lead to the formation of AVIs. Therefore, the type of decoration mainly aromatic acylation of anthocyanins is responsible for AVI formation. From understanding the molecular mechanisms of acyltransferases for side chain decoration to their activity, anthocyanins can be engineered by anthocyanin acyltransferases in plants for novel functionalities. I showed that coumaroylation of anthocyanins promotes copigmentation more effectively than 5-glucosylation. 5- glucosylation, together with coumaroylation, offered stability to anthocyanins, both invitro and in-vivo. I also showed that flavonols copigment better than phenolics with anthocyanins, a property which could be useful for developing natural food colours. Thus, my study provided an in-depth investigation from molecular mechanisms to final applications of side chain decoration of anthocyanins.

The work presented in this thesis deals with the analysis of protein crystal structures with an emphasis on the stereochemical aspects of the folded conformation of proteins. The various analyses described have been performed on a data-set of 250 high resolution and non-homologous protein structures derived from the Protein Data Bank. The overall objective of the work has been to analyse conformational features of the non-secondary structural regions in proteins and identify structural motifs present therein. The results can be useful in the three-dimensional modelling of proteins, altering the stability of proteins, design of peptide mimics and in understanding the structural rules that guide protein folding. The contents of this thesis can be broadly classified into three parts, (a) Conformational preferences of amino acid residues to occur in the partially allowed regions of the Ramachandran map, (b) conformational features of structural motifs formed by side-chain/main-chain hydrogen bonds by polar residues and (c) analysis and characteristic features of isolated β-strands. Chapter 1 of the thesis gives an introduction, briefly discussing the conformation of polypeptide chains, structural features of globular proteins and applications of protein structural analysis etc. Chapter 2 describes the occurrence of left-handed α-helical conformation in protein structures. A data-set of 250 high resolution (< 2.0A) non-homologous protein crystal structures derived from the Protein Data Bank (PDB) has been analysed for occurrences of left-handed α-helical (αL) conformations. A total of 2,573 αL residues were identified from the data-set. About 59% of the observed examples of at conformations were found to be glycyl residues and about 41% non-glycyl. Continuous long stretches of αL residues are seldom found in protein structures. They are most commonly found as singlets represented by 78% of the observed αL examples. The doublets, triplets and quadruplets account for a very minor fraction of the observed examples. There is only a single example of a stretch of four contiguous αL residues, from the protein thermolysin, which forms a single turn of a left-handed α-helix. A majority of the αL residues are nevertheless part of well-defined substructures in proteins. They play singular roles as part of β-turns and helix termination sites in maintaining the characteristic main-chain hydrogen bonds needed for the stability of these structures. They are also found to be effective in the termination of β-strands. The stereo-chemistry and sequence environment around such structures are discussed. The analysis of the side-chain torsion angles of αL residues indicate that the g+ rotamer is highly unfavourable due to stereo-chemical violations posed by the atoms of the side-chain with those of the backbone. The αL residues are highly conserved by residue type as well as conformation among related proteins indicating their vital importance in protein structures Chapter 3 provides an explanation for the unusual preference of glycyl residues to occur in the bridge regions of the Ramachandran map. The Ramachandran steric map and energy diagrams for the glycyl residue are fully symmetric. Though a plot of the (Φ,Ψ) angles of glycyl residues derived from a data-set of 250 non-homologous and high-resolution protein structures is also largely symmetric, there is a clear aberration in the symmetry. While there is a cluster of points corresponding to the right-handed a-helical region, the "equivalent" cluster is shifted to centre around the (Φ,Ψ)values of (90°, 0°) instead of being centred at the left-handed a-helical region of (60°, 40°). An analysis of glycyl conformations in small peptide structures and in "coil" proteins, which are largely devoid of helical and sheet regions, shows that glycyl residues prefer to adopt conformations around (±90°, 0°) instead of right and left handed a-helical regions. Using theoretical calculations, such conformations are shown to have highest solvent accessibility in a system of two-linked peptide units with glycyl residue at the central Cα atom. This is found to be consistent with the observations from 250 non-homologous protein structures where glycyl residues with conformations close to (±90°, 0°) are seen to have high solvent accessibility. Analysis of a sub-set of non-homologous structures with very high resolution (1.5A or better) shows that water molecules are indeed present at distances suitable for hydrogen bond interaction with glycyl residues possessing conformations close to (±90°, 0°). It is concluded that water molecules play a key role in determining and stabilising these conformations of glycyl residues and explains the aberration in the symmetry of glycyl conformations in proteins. Chapter 4 discusses an analysis of backbone mimicry performed by polar side-chains in protein structures. Backbonemimicry bythe formation of closed loop C7, C10, C13 (mimics of γ-, β- and α-turns) conformations through side-chain main-chain hydrogen bonds by polar groups is found to be a frequent observation in protein structures. A data-set of 250 non-homologous and high-resolution protein structures was used to analyse these conformations for their characteristic features. Seven out of the nine polar residues (Ser, Thr, Asn, Asp, Gin, Glu and His) have hydrogen bonding groups in their side-chains which can participate in such mimicry and as many as 15% of all these polar residues engage in such conformations. The distributions of dihedral angles of these mimics indicate that only certain combinations of the involved dihedral angles aids the formation of these mimics. The observed examples have been categorised into various classes based on these combinations resulting in well-defined motifs. Asn and Asp residues show a very high capability to perform such backbone secondary structural mimicry. The most highly mimicked backbone structure is of the Cio conformation by the Asx residues. The mimics formed by His, Ser, Thr and Glx residues are also discussed. The role of such conformations in initiating the formation of regular secondary structures during the course of protein folding seems significant. Chapter 5 presents a description of deterministic features of side-chain main-chain hydrogen bonds as observed in protein structures. A total of 19,835 polar residues from the data set of 250 non-homologous and highly resolved protein crystal structures were used to identify side-chain main-chain (SC-MC) hydrogen bonds. The ratio of the total number of polar residues to the number of SC-MC hydrogen bonds is close to 2:1, indicating the ubiquitous nature of such hydrogen bonds. Close to 56% of the SC-MC hydrogen bonds are local involving side-chain acceptor/donor (‘i’) and a main-chain donor/acceptor within the window i-5 to i+5. These short-range hydrogen bonds form well defined conformational motifs characterised by specific combinations of backbone and side-chain torsion angles. Some of the salient features of such hydrogen bonds are as follows, (a) The Ser/Thr residues show the greatest preference in forming intra-helical hydrogen bonds between the atoms Oyi and Oi-4 Such hydrogen bonds form motifs of the form αRαRαRαR(g") and are most commonly observed at the middle of α-helices. (b) These residues also show great preference to form hydrogen bonds between OYi and Oi-3, which are closely related to the previous type and though intra-helical, these hydrogen bonds are more often found at the C-termini of helices than at the middle. The motif represented by αRαRαRaR(g+) is most preferred in these cases, (c) The Ser, Thr and Glu (between the side-chain and main-chain of the same residue), (d) The side-chain acceptor atoms of Asn/Asp and Ser/Thr residues show high preference to form hydrogen bonds with acceptors two residues ahead in the chain, which are characterised by the motifs β(tt’)αR and β(t)αR, respectively. These hydrogen bonded segments referred to as Asx turns, are known to provide stability to type I and type I’ β-turns. (e) Ser/Thr residues often form a combination of SC-MC hydrogen bonds, with the side-chain donor hydrogen bonded to the carbonyl oxygen of its own peptide backbone and the side-chain acceptor hydrogen bonded to an amide hydrogen three residues ahead in the sequence. Such motifs are quite often seen at the beginning of a-helices, which are characterised by the β (g+)αRαR motif. A remarkable majority of all these hydrogen bonds are buried from the protein surface, away from the surrounding solvent. This strongly indicates the possibility of side-chains playing the role of the backbone, in the protein interiors, to satisfy the potential hydrogen bonding sites and maintaining the network of hydrogen bonds which is crucial to the structure of the protein. Chapter 6 provides a detailed characterisation of isolated β-strands. Reason for the formation of β-strands in proteins is often associated with the formation of β -sheets. However β-strands, not part of β-sheets, commonly occur in proteins. This raises questions about the structural role and stability of such isolated β-strands. Using a data set consisting of 250 proteins, 518 isolated β-strands have been identified from 187 proteins. The two important features that distinguish isolated β-strands from p-strands occurring in β-sheets are (i) the high preponderance of prolyl residues to occur in isolated β-strands and (ii) their high solvent exposure. It is shown that the high propensity for proline residues to occur in isolated β-strands is not due to the occurrence of polyproline type segments in the data-set. The propensities of other amino acids to occur in isolated β-strands follows the same trend as those for β-sheet forming β-strands. Isolated β-strands are characterised often by their main-chain amide and carbonyl groups involved in hydrogen bonding with polar side-chains or water. They are often flanked by irregular loop structures indicating that they are part of long of loops. Analysis of the conservation of such strands among families of homologous protein structures indicates that a sizeable fraction of them are highly conserved. It is suggested that though the formation of isolated β-strands are driven by the intrinsic preferences of amino acid residues, they have many characteristics like loop segments but with repetitive (Φ,Ψ) values falling within the β-region of the Ramachandran map. In addition of the material described in the six chapters above, the thesis also contains the details of work carried out on an aspect slightly different from the main theme of the thesis. This pertains to the comparative analysis of the members of a family of cytokine receptors to derive information to model new members of the family. The three dimensional modelling of the leptin receptor has been used as a case study and the details are included as an appendix. Appendix describes the 3-dimensional model of the satiety factor receptor (the leptin receptor) modelled using principles of homology modelling. Recessive mutations in the mouse obese (ob) and diabetes (db) genes result in obesity and diabetes in a syndrome resembling human obesity. Data from parabiosis (cross circulation) experiments suggested that the ob gene coded, and was responsible for the generation of a circulating factor called leptin which regulated energy balance and the db gene encoded the receptor for this factor. While the structure of the leptin has been determined that of its cognate receptor is as yet unknown. The leptin receptor shows low but clear sequence similarity to the members of the interleukin type 6 family of receptors. The structures of the members of this family are characterised by two p-sandwich like domains connected by a short 4-residue helical linker. The 3-dimensional models for the N- and C-terminal domains of the leptin receptor was generated using the corresponding structures of the signal transducing component of gpl30, the erythropoetin receptor and the prolactin receptor. Further using the evidence that the leptin binds to its receptor with a stoichiometry of 1:1, the relative orientation of the two domains was modelled based on the structure of the human growth hormone receptor, which also binds its ligand with similar stoichiometry. The complex of leptin with its receptor was also modelled based on the structure of human growth hormone/receptor complex. The final energy minimised model of the complex elucidates the mode of interaction between the leptin and its receptor.

AbstractChickpea (Cicer arietinum L.) is the third important food legume both in area and production after common beans and faba beans in Ethiopia. However, the productivity of the crop was very low compared to the potential as a result of non-use of improved varieties and technologies generated by the research system. To enhance the use of the improved and associated research technologies a National Chickpea Stakeholders Innovation Platform was established in 2013 with the objective of bringing together various stakeholders acting on the value chain in order to identify major challenges and find solutions that would be implemented through synergetic efforts. The platform identified seed shortage as a major bottleneck in the sector. This issue has been addressed through establishing farmers’ seed producer associations with the help of R&D partners and currently they are the major suppliers nationwide. Side by side, the platform strengthened the extension effort and triggered dissemination of improved technologies to a large number of farmers. As a result, productivity of the crop by model farmers increased by fourfold and the national productivity has been doubled to 2 ton ha−1 in the last decade. The platform also worked on improving access to market and recently chickpea joined the Ethiopian Commodity Exchange market. Cognizant of the huge development potential of the crop, the platform is striving to further strengthen the intervention and reap opportunities.

Abstract It is known to all that there is the polygon effect in chain drives, it causes that the velocity ratio transmitted changes periodically, and the velocity of driven sprocket is variational, while the velocity of driving sprocket is constant in chain drives. For reducing the effect a new method simple in construction is developed in this paper — with a tensioner which is mounted in the proper position at the tight side, the variation of velocity ratio transmitted and the velocity of driven sprocket can be reduced evidently. In this paper it has been discussed how to determine the position and the teeth number of the tensioner in order to reduce the variation of transmition ratio in the chain drives. In addition, an example is presented here, it can be indicated that the variation of velocity ratio transmitted can be reduced evidently by use of the method with a tensioner at the tight side.

Decentralized production systems in supply chains / networks makes them more profitable and agile than traditional enterprises with centralized production systems. However, this decentralization makes supply chains / networks more vulnerable respect to uncertainties which are unavoidable. Today’s supply chains / networks producing and supplying their products to markets are characterized by uncertain demands (called demand-side uncertainty) and uncertainties associated with the performances of their constituent production facilities (called supply-side uncertainty). Supply-side uncertainty is due to the fact that there is not any perfect production system. Sparse literature of supply-side uncertainty management in supply chains / networks is only restricted to supply chains / networks with single-echelon supply processes. However most of the real case supply chains / networks have longer production processes involving suppliers of suppliers, suppliers, component manufacturers, assemblers, etc. In this paper we fill this gap of the literature by considering a supply chain/network with multi-echelon supply process including unreliable production facilities working in markets with uncertain demands. We show that in such a complex production process in addition to investigating the local effects of the uncertainties in the performances of their corresponding facilities, it is necessary to consider their global and cumulative effect on the performance of the entire supply chain/networks by following the propagation of these uncertainties in the flow of the material and product. Not only we introduce and describe the salient features of uncertainty propagation phenomenon in supply chains/networks, but also we demonstrate its quantification approach. Finally we propose mathematical models and solution approaches that can provide robust production plans for the supply chain/network that are protected against all demand and supply side uncertainties and their propagated effects. Performances of the proposed models and solution approaches are tested with test problems and a real case problem from automotive industry.

Pro-urokinase (PUK) has been reported to bind to fibrin-Sepharose specifically but not to fibrin clot. As thrombin (TH) clotted fibrinogen and cleaved the Arg 156-Phe 157 peptide bond of PUK simultaneously, we tested effect of this cleavage on the binding of PUK to fibrin by using high molecular weight urokinase (HMUK), PUK purified from culture media of human kidney cell (nPUK) and two kinds of recombinant PUK (rPUK) expressed in genetically transformed E. Coli. One rPUK designated as P0 lacks the carbohydrate side chain present in nPUK but has the same amino acids sequence as nPUK does. The other rPUK designated as P3 is a mutant whose Phe 157 was replaced by Asp so as to be resistant against the proteolytic cleavage by TH. The rate of conversion of single-chain 125I labeled PUK (125I PUK) to two-chain form by TH or plasmin (PM) was determined by both amidolytic activity toward S-2444 and autoradiography of polyacrylamide gel under reducing conditions. Although 100 U/ml TH did not cleave 125I P3 in 2h at 37°C, 10 U/ml TH completely cleaved H00 U/ml 125I nPUK and PO instantaneously. 125I PUK, which had been totally or partially cleaved by either TH or PM, was mixed with fibrinogen in the presence of aprotinin. Then the mixture was clotted with 2.5 mM Ca2+ and 0.5 U/ml TH which cleaved PUK only a little for 10 min. Clots were obtained by clot-syneresis and washed with Tris-buffer containing albumin, aprotinin and hirudin. The bound PUK was calculated by measuring the radioactivity of the clot and the supernatant. Although the binding of nPUK and PO to fibrin decreased from 12% to 1% as cleavage by TH or PM proceeded, that of P3 to fibrin decreased only when two-chain conversion was processed by PM. HMUK did not bind to fibrin. These results strongly suggest that single-chain PUK binds to fibrin and imply that P3, which is TH-resistant, may be useful as an activator in the presence of TH surrounding the clot.

The purpose of this study was to understand how the side group dictates thermo-mechanical properties of shape-memory acrylate networks, specifically strain to failure and toughness. A useful parameter in assessing shape memory polymers is the strain to failure because it is critical to know how much recovery strain the material can experience. To understand how the structure is related to mechanical properties, such as strain to failure, materials of differing chain stiffness ratio, C∞, were compared at varying percentages of crosslinker. While the chemical and thermal properties of acrylate networks have been discussed in much detail, methods of toughening networks by the precise choice of certain acrylates have not been thoroughly examined. In order for these networks to be of practical use as biomedical devices, such as minimally invasive shape memory polymer stents, detailed structure-property relationships must be established.

The primary objective of the present study is to investigate the influence of the molecular structure (linear or with bulky side groups) of polymer films (of few nanometers thickness) covalently attached to Si surface on tribological properties. PE (polyethylene) and PS (Polystyrene) were selected to test the objective where PE has simple linear molecular structure while PS also has linear molecular structure but contains bulky benzene groups located at the side of the linear chain. PE and PS contains maleic anhydride groups and are chemisorbed onto the APTMS (3-aminopropyltrimethoxysilane) modified Si surface. AFM (atomic force microscopy), XPS (X-ray photoelectron microscopy) and water contact angle measurements are used to identify and characterize the polymer films. A micro-tribometer is used to identify the tribological properties in a sliding test using 4 mm diameter Si3N4 ball as the counterface. PE film has shown very low coefficient of friction and high wear durability when compared to PS film and moreover PS film did not show any improvement in the tribological properties when compared to bare Si surface. This study proves that even in film form polymer with linear molecular structure without the bulky side groups show good tribological properties and hence such polymers can be used as thin-films for reducing friction and wear of substrates, Si or other materials. The chemisorbed PE film may be able to find applications in micro-components made from Si surface as anti-stiction and anti-wear coating.

The standard chain lever load binder that is used for truck cargo securement operates on an over-center principle that has been used for over a century on suitcases, tool boxes and camera cases. The safety hazards associated with the uses and misuses of the load binder were identified decades ago and various inventors patented innovations that eliminated or mitigated the safety shortcomings. Furthermore, their ideas were not only effective, they were economical, versatile, and efficient. These patents are now in the public domain and many companies manufacture and/or distribute entire lines of securement that include not only the standard chain lever load binder but most of the alternative designs as well. This case study takes the position that the standard chain lever load binder should be banished. Since the appropriate bodies, after all these years, have not arranged for its demise, this paper appeals to the product liability system for safety relief. Engineering analysis and tests are provided to the legal profession to help them protect us by making the cost advantage of the standard binder too expensive. This paper explores some of the remarkable properties of the standard load binder, e.g., • Load binders develop very large chain tensions and very high levels of recoverable energy. The standard chain lever load binder does not enable the tension and energy levels to be safely maintained or released. • The handle slack on the standard load binder cannot be fine-tuned; consequently, a scenario is frequently encountered where the chain is either too loose or too tight to secure with the binder handle. This is the major motivation for resorting to a “cheater bar.” • A complete analysis of the securement forces acting on the cargo and load binder is seldom possible because the system is a “moving target.” The handle loading is randomly applied by human exertion which changes with handle orientation. The boundary conditions depend not only on the cargo and securement strategy, but on the loading itself. Unknown friction characteristics of the loading affect the distribution of chain forces. • On one side of the load binder the chain tension can always be predicted using only the handle torque. This cable tension is independent of the boundary conditions and any axial handle force components. • When the load binder system is rigid, it gives rise to three singularities. The mechanical advantage is unbounded at the two extreme handle orientations. When the binder is suspended in a taut condition, any lateral force on the binder develops infinite cable forces. • Handle slack has a profound effect on the handle resistance, the resilience, the chain tension, and the latching capability.

In this paper we investigate how the fiscal authorities, through tax policies or fiscal incentives, can play an important role in supporting digitalisation of the economy (digital transformation) to exploit its opportunities. Our approach is to track the influence of these policies indirectly through relevant determinants of internet adoption (connectivity and user enablers). Hence, we first establish empirically the influence of these enablers on internet use by estimating a reduced form equation of determinants of internet adoption (both demand- and supply-side factors). Then we assess the influence of a country’s fiscal policy stance on some of these enablers or determinants (direction and extent) throughout the internet value chain. Using these transmission mechanisms, we estimate the influence of the fiscal regime on digitalisation. We draw on our own empirical analysis and other relevant studies to support our recommendations to the fiscal authorities. Our findings emphasise the importance of trade-offs between short-term revenue objectives and the longer-term opportunity costs of higher revenue, enabled by the large positive externality effects of the sector, generating higher social returns than those accruing privately.

The power and promise of genome editing, CRISPR specifically, was first realized with the discovery of CRISPR loci in the 1980s.i Since that time, CRISPR-Cas systems have been further developed enabling genome editing in virtually all organisms across the tree of life.i In the last few years, we have seen the development of a diverse set of CRISPR-based technologies that has revolutionized genome manipulation.ii Enabling a more diverse set of actors than has been seen with other emerging technologies to redefine research and development for biotechnology products encompassing food, agriculture, and medicine.ii Currently, the CRISPR community encompasses over 40,000 authors at 20,000 institutions that have documented their research in over 20,000 published and peer-reviewed studies.iii These CRISPR-based genome editing tools have promised tremendous opportunities in agriculture for the breeding of crops and livestock across the food supply chain. Potentially addressing issues associated with a growing global population, sustainability concerns, and possibly help address the effects of climate change.i These promises however, come along-side concerns of environmental and socio-economic risks associated with CRISPR-based genome editing, and concerns that governance systems are not keeping pace with the technological development and are ill-equipped, or not well suited, to evaluate these risks. The Inter-American Development Bank (IDB) launched an initiative in 2020 to understand the complexities of these new tools, their potential impacts on the LAC region, and how IDB may best invest in its potential adoption and governance strategies. This first series of discussion documents: “Genome Editing in Latin America: Regulatory Overview,” and “CRISPR Patent and Licensing Policy” are part of this larger initiative to examine the regulatory and institutional frameworks surrounding gene editing via CRISPR-based technologies in the Latin America and Caribbean (LAC) regions. Focusing on Argentina, Bolivia, Brazil, Colombia, Honduras, Mexico, Paraguay, Peru, and Uruguay, they set the stage for a deeper analysis of the issues they present which will be studied over the course of the next year through expert solicitations in the region, the development of a series of crop-specific case studies, and a final comprehensive regional analysis of the issues discovered.

The power and promise of genome editing, CRISPR specifically, was first realized with the discovery of CRISPR loci in the 1980s.3 Since that time, CRISPR-Cas systems have been further developed enabling genome editing in virtually all organisms across the tree of life.3 In the last few years, we have seen the development of a diverse set of CRISPR-based technologies that has revolutionized genome manipulation.4 Enabling a more diverse set of actors than has been seen with other emerging technologies to redefine research and development for biotechnology products encompassing food, agriculture, and medicine.4 Currently, the CRISPR community encompasses over 40,000 authors at 20,000 institutions that have documented their research in over 20,000 published and peer-reviewed studies.5 These CRISPR-based genome editing tools have promised tremendous opportunities in agriculture for the breeding of crops and livestock across the food supply chain. Potentially addressing issues associated with a growing global population, sustainability concerns, and possibly help address the effects of climate change.4 These promises however, come along-side concerns of environmental and socio-economic risks associated with CRISPR-based genome editing, and concerns that governance systems are not keeping pace with the technological development and are ill-equipped, or not well suited, to evaluate these risks. The Inter-American Development Bank (IDB) launched an initiative in 2020 to understand the complexities of these new tools, their potential impacts on the LAC region, and how IDB may best invest in its potential adoption and governance strategies. This first series of discussion documents: “Genome Editing in Latin America: Regulatory Overview,” and “CRISPR Patent and Licensing Policy” are part of this larger initiative to examine the regulatory and institutional frameworks surrounding gene editing via CRISPR-based technologies in the Latin America and Caribbean (LAC) regions. Focusing on Argentina, Bolivia, Brazil, Colombia, Honduras, Mexico, Paraguay, Peru, and Uruguay, they set the stage for a deeper analysis of the issues they present which will be studied over the course of the next year through expert solicitations in the region, the development of a series of crop-specific case studies, and a final comprehensive regional analysis of the issues discovered.