A rapid library screen for tailoring beta-peptide structure and function.
J Am Chem Soc
; 127(42): 14584-5, 2005 Oct 26.
Article
in En
| MEDLINE
| ID: mdl-16231906
ABSTRACT
Recently we described a beta-decapeptide (beta53-1) that folds into a 14-helix in aqueous solution, binds the oncoprotein hDM2 with submicromolar affinity, and inhibits the interaction of hDM2 with a peptide derived from the activation domain of p53 (p53AD). The solution structure of beta53-1 in CD3OH revealed an unexpected C-terminal unwinding that staggers the side chains comprising the hDM2 recognition epitope to better mimic those of p53AD. The structure-function relationship implied by this distortion suggested that a library of beta53-1 analogues possessing diversity along a nonrecognition face might contain molecules possessing greater affinity for hDM2. Here we describe (1) beta-peptide synthesis protocols that produce high quality one-bead-one-beta-peptide libraries suitable for on-bead screening without purification, (2) a versatile, scalable on-bead screen, and (3) a simple tandem mass spectrometry (MS/MS) decoding method. Using this procedure, we identified beta53-1 analogues with improved structural and functional properties.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peptide Fragments
/
Peptide Library
Language:
En
Journal:
J Am Chem Soc
Year:
2005
Document type:
Article
Affiliation country:
Estados Unidos