Identification of novel low molecular weight CXCR4 antagonists by structural tuning of cyclic tetrapeptide scaffolds.
Publication/Presentation Date
5-5-2005
Abstract
A highly potent CXCR4 antagonist, compound 2, was previously found by using two orthogonal cyclic pentapeptide libraries involving conformation-based and sequence-based libraries based on the pharmacophore of a 14-mer peptidic antagonist, 1. Herein, cyclic tetrapeptides derived from replacements of the dipeptide unit (Nal-Gly) with a gamma-amino acid and pseudopeptides cyclized by disulfide and olefin bridges were synthesized to find novel scaffold structures different from that of cyclic pentapeptides. These compounds contain a reduced number of peptide bonds compared to compound 2. Furthermore, several analogues with chemical modification of the side chain of Arg(4) in 2 were also prepared. From these, several new leads possessing high to moderate CXCR4-antagonistic activity were characterized.
Volume
48
Issue
9
First Page
3280
Last Page
3289
ISSN
0022-2623
Published In/Presented At
Tamamura, H., Araki, T., Ueda, S., Wang, Z., Oishi, S., Esaka, A., Trent, J. O., Nakashima, H., Yamamoto, N., Peiper, S. C., Otaka, A., & Fujii, N. (2005). Identification of novel low molecular weight CXCR4 antagonists by structural tuning of cyclic tetrapeptide scaffolds. Journal of medicinal chemistry, 48(9), 3280–3289. https://doi.org/10.1021/jm050009h
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
15857134
Department(s)
Administration and Leadership
Document Type
Article