Peptide combinatorial library screening

A very powerful method for screening active peptides without knowing the actual sequence is the combinatorial peptide library. This method was first described by Houghten and coworkers for peptides synthesized on a polymer resin (53). Using combinatorial libraries, screening begins in theory... 

Eichler J, Houghten RA, Identification of substrate-analog trypsin inhibitors through the screening of synthetic peptide combinatorial libraries, Biochemistry, 32(41) 11035—41, 1993. 

Stevenson CL, Augustijns PF, Hendren RW (1995) Peremabil-ity screen for synthetic peptide combinatorial libraries using CACO-2 cell monolayers and LC-MS/MS. Pharm Res 12 94... 

It is important to further develop the concept of structure-activity relationships to precisely define the structural requirements of glutathione action. Thus, this section introduces the design, synthesis, and screening of a peptide combinatorial library to obtain multiple glutathione analogs. Combinatorial libraries will be composed of mixtures of peptides (consisting of natural or noncoded amino acids) on solid support. After cleavage from the resin, the mixtures of the peptides will be screened directly in different specific assays. 

Peptidomimetic ligands for opioid receptors have also been identified from combinatorial libraries. Screening of an N-(substi-tuted)glycine peptoid library for affinity for ix opioid receptors yielded novel structures (251) with high affinity for these receptors (K = 6-46 nM) (953). A library of dipeptide amides with alkyl substituents on both the interior and C-terminal amides were prepared, and high affinity agonists for all three opioid receptors identified from the library (see Ref 946). Peptide libraries can also be further modified ["libraries from libraries" (954)] to yield new potential ligands for receptors. Thus an acety-... 

Stevenson, C., Augustijns, P. and Hendren, R. (1999) Use of Caco-2 cells and LC/MS/MS to screen a peptide combinatorial library for permeable structures. International Journal of Pharmaceutics, 15, 103—115. 

Wigger, M. Eyler, J.R. Benner, S.A. Li, W. Marshall, A.G. Fourier Transform-Ion Cyclotron Resonance Mass Spectrometric Resolution, Identification, and Screening of Non-Covalent Complexes of Hck Src Homology 2 Domain Receptor and Ligands from a 324-Member Peptide Combinatorial Library, J. Am. Soc. Mass Spectrom. 13, 1162-1169 (2002). 

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