Scaffolded multiple cyclic peptide libraries for protein mimics by native chemical ligation.
The accessibility to collections, libraries and arrays of cyclic peptides is increasingly important since cyclic peptides may provide better mimics of the loop-like structures ubiquitously present in and - especially - on the surface of proteins. The next important step is the preparation of libraries of ensembles of scaffolded cyclic peptides, which upon screening may lead to promising protein mimics. Here we describe the synthesis of a tri-cysteine containing scaffold as well as the simultaneous native chemical ligation of three cyclic peptides thereby affording a clean library of multiple cyclic peptides on this scaffold, representing potential mimics of gp120. Members of this collection of protein mimics showed a decent inhibition of the gp120-CD4 interaction.
Medicinal Chemistry & Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Department of Pharmaceutical Sciences, Faculty of Sciences, Utrecht University, P.O. Box 80082, 3508 TB, Utrecht, The Netherlands. r.m.j.liskamp@uu.nl.
H
H
van de Langemheen
M
M
van Hoeke
H C
HC
Quarles van Ufford
J A W
JA
Kruijtzer
R M J
RM
Liskamp
D000595:Amino Acid Sequence; D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry; D001665:Binding Sites; D001671:Biochemistry / Q000379:methods*; D015704:CD4 Antigens / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry; D015699:HIV Envelope Protein gp120 / Q000737:chemistry; D006574:Heterocyclic Compounds, 2-Ring / Q000138:chemical synthesis / Q000737:chemistry; D008969:Molecular Sequence Data; D019151:Peptide Library; D010456:Peptides, Cyclic / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*
D001372:Aza Compounds; D015704:CD4 Antigens; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D006574:Heterocyclic Compounds, 2-Ring; D019151:Peptide Library; D010456:Peptides, Cyclic; D011506:Proteins; C539946:triazacyclophane