The synthesis of peptidomimetic combinatorial libraries through successive amide alkylations.
A soluble peptidomimetic combinatorial library of 57,500 compounds was prepared. This library has a dipeptide scaffold with each amide hydrogen replaced with five different alkyl groups (methyl, ethyl, allyl, benzyl, or naphthylmethyl). Solid-phase methodology in combination with N-alkylation were used to synthesize the library, which incorporated 50 different L-, D-, and unnatural amino acids. Repetitive amide alkylations were carried out on the solid support following each amino acid coupling step. Individual model compounds were synthesized in order to optimize the alkylation conditions, to study potential amino acid side chain modifications, to determine the extent of racemization, and to provide analytical controls during the library synthesis.
Dörner
B
B
Torrey Pines Institute for Molecular Studies, San Diego, CA 92121, USA.
Husar
G M
GM
Ostresh
J M
JM
Houghten
R A
RA
D000478:Alkylation; D000577:Amides / Q000737:chemistry*; D000596:Amino Acids / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004151:Dipeptides / Q000138:chemical synthesis*; D005449:Fluorenes / Q000737:chemistry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000577:Amides; D000596:Amino Acids; D004151:Dipeptides; D005449:Fluorenes; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids