Molecular‐Size Reduction of a Potent CXCR4‐Chemokine Antagonist Using Orthogonal Combination of Conformation‐ and Sequence‐Based Libraries

Abstract

Efficient downsizing of peptides: By combination of two orthogonal “conformation-based” and “sequence-based” libraries, the cyclic pentapeptide cyclo(-L-Nal 1-Gly 2-D-Tyr 3-L-Arg 4-L-Arg 5-) (Nal=L-3-(2-naphthyl)alanine; see overlay of the five lowest energy structures), which exhibited strong CXCR4 antagonism (IC50=4 nM) comparable to that of a 14-residue lead compound, T140, was discovered. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2003/z51024_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.