Sequence-selective nonmacrocyclic two-armed receptors for peptides

Nestler, H. P. (October 1996) Sequence-selective nonmacrocyclic two-armed receptors for peptides. Molecular Diversity, 2 (1-2). pp. 35-40. ISSN 1381-1991 (Print)

URL: http://www.ncbi.nlm.nih.gov/pubmed/9238631
DOI: 10.1007/BF01718698

Abstract

Tweezer-like receptor molecules have proven their potential for molecular recognition on several occasions. We decided to make twofold use of this receptor design: firstly to learn whether simple molecular forceps consisting of two peptide chains linked by a spacer are able to selectively bind to small peptides, and secondly to investigate the importance of structural preorganization for the characteristics of the receptors. We prepared two encoded combinatorial libraries based on this design, featuring two combinatorial tripeptide chains held by different scaffolds: the use of chenodeoxycholic acid as spacer provided a rigid scaffold for the forceps, whereas linking the peptide chains by a pentamethylene chain yielded a very flexible forceps structure. Molecules from the cholic acid library recognize and discriminate various enkephalins with micromolar affinities. Molecules from the flexible library show distinct interactions with the enkephalins as well, but the specificity and affinity are clearly diminished. Thus, although the interactions of molecular forceps with peptides are not crucially dependent on structural preorganization, receptors with a rigid design are clearly superior to flexible molecular forceps.

Item Type: Paper
Uncontrolled Keywords: Amino Acid Sequence Peptide Library Peptides/ chemistry/metabolism Peptides, Cyclic/chemistry Protein Binding Receptors, Peptide/agonists/antagonists & inhibitors/ chemistry Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Structure-Activity Relationship
Subjects: bioinformatics > genomics and proteomics > design > protein network design > peptide design
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein receptor
CSHL Authors:
Communities: CSHL labs > Nestler lab
Depositing User: Matt Covey
Date: October 1996
Date Deposited: 22 May 2014 14:05
Last Modified: 22 May 2014 14:05
Related URLs:
URI: http://repository.cshl.edu/id/eprint/30177

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