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Abrf poster with legend with links

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In order to induce structural conformation in peptides many scientists …

In order to induce structural conformation in peptides many scientists
have utilized cyclization due to the versatile methods of peptide synthesis
and availability of protecting groups which can be orthogonally removed.
Constrained peptides have been shown to have improved the biological
properties compared to the linear peptides.

Published in: Health & Medicine
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  • 1. Applications of Constrained Peptides to Various Biological Processes Eunice Murage, Ph.D. and Miguel Castro, Ph.D. Protein Chemistry, Bio-Synthesis, Inc., Lewisville, Texas 75057 O R2 O R4 OIntroduction H H N H N N N In order to induce structural conformation in peptides many scientists H N R1 O R3 H O R5have utilized cyclization due to the versatile methods of peptide synthesis Hydrocarbon stapling using Lactam bridge formationand availability of protecting groups which can be orthogonally removed. ring closing metathesisConstrained peptides have been shown to have improved the biological NH Backboneproperties compared to the linear peptides. Cyclization O For example, cyclic peptides have shown: 1. Enhanced receptor affinity and efficacy O 2. Improved cell permeability and enzyme stability R5 R1 H nk er In addition, these constraints provide a conceptual approach towards Li HN Odesigning of peptidomimetics. NClassic Examples Hydrocarbon Stapled Peptides O NH HN R4 Lactam Bridge Peptides H Peptide Type of Modification Properties R2 N R3 O α - Conotoxin N- to C- terminus cyclization Increased stability in human plasma1 O Hydrocarbon stapling Increased protease resistance BID BH3 Head to tail/ end to side chain cyclization using ring closing metathesis and serum stability2 Hydrocarbon stapling Increase binding affinity towards Conclusion: NOTCH1 using ring closing metathesis NOTCH transactivation complex3 It is scientifically evidenced that constrained peptides in form of stapled or lactam-bridged DP178 Side chain to side chain i, Increase HIV inhibitory activity as a have attractive biological properties superior to their linear counterparts and introduced a (HIV35) i+7 lactam bridge formation result of stabilized α-helical conformation4 unique technique for studying protein-protein interactions which mediates most of biological actions. In order to further study peptides with these promising properties, BIOSYNTHESIS, INC. has recently launched a peptide conformation screening tool called positional cyclization Acknowledgement: scanning. fd I would like to thank Ian Flynn and Heidi Fazeli and for design and support. This technique is aimed at identifying the receptor-bound conformation of various biological References: peptides by constraining specific segment of the peptide and studying its effect on the biological 1. Clark et al. Proc Natl Acad Sci USA 2005, 102, 13767–13772. activity. 2. Walensky et. al., Science, 2004, 3, 1466-1470 3. Raymond et. al., Nature 2009, 462, 182-188. 4. Judice et. al., Proc. Natl. Acad. Sci. USA. 1997, 94, 13426-13430 www.biosyn.com Service across Genomics, Proteomics and Cell Biology Toll Free: 800.227.0627 | 972.420.8505 Mail: info@biosyn.com

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