Peptide libraries: Determination of relative reaction rates of protected amino acids in competitive couplings Article

Ostresh, JM, Winkle, JH, Hamashin, VT et al. (1994). Peptide libraries: Determination of relative reaction rates of protected amino acids in competitive couplings . BIOPOLYMERS, 34(12), 1681-1689. 10.1002/bip.360341212

cited authors

  • Ostresh, JM; Winkle, JH; Hamashin, VT; Houghten, RA

authors

abstract

  • In the solid phase preparation of synthetic peptide libraries, equimolarity of the resultant peptides in the mixture simplifies the identification of active compounds. Two primary methods for the preparation of combinatorial peptide mixtures are currently used. In the first method, the starting resin is divided into equal aliquots, individual amino acids are coupled to each aliquot, and the resin is then recombined. This process is repeated for each position. However, due to the physical process, each resin bead contains only one peptide sequence. Statistically, for mixtures of longer sequences, an ever‐increasing amount of resin is necessary to ensure complete representation of each peptide in the library. Thus, each peptide will be represented in the library if a sufficient number of resin beads are used. In addition, the concentration of each peptide in the library depends on both the number of mixture positions in the library and the amount of resin used. In the second method, mixtures of amino acids are coupled simultaneously at each addition step. The proportion of each amino acid in the reaction mixture is varied inversely to its reaction rate such that, ideally, an equimolar mixture of each peptide is synthesized. An advantage of this method over the previous method is that each peptide is ensured to be represented in the library, although not necessarily in equimolar amounts. It is known that not only do the coupling rates of each amino acid vary, but the coupling rates of individual amino acids also change when coupled to different amino acid resins. Consequently, in order to obtain equimolar peptide mixtures through the use of mixtures of protected amino acids, the ratio of reaction rates of one amino acid over another must be constant irrespective of the resin‐bound amino acid. If this premise is true, this method of synthesis offers a significant advantage over the previous method since, theoretically, equimolar peptide libraries could be synthesized. The influence of the resin‐bound amino acid on the relative reaction rates of incoming amino acids was investigated in the current study. © 1994 John Wiley & Sons, Inc. Copyright © 1994 John Wiley & Sons, Inc.

publication date

  • January 1, 1994

published in

Digital Object Identifier (DOI)

start page

  • 1681

end page

  • 1689

volume

  • 34

issue

  • 12