Peptide combinatorial library applications

MA Gallop, RW Baii et, WJ Dower, SPA Fodor, EM Gordon. Applications of combinatorial technologies to drug discovery. 1. Background and peptide combinatorial libraries. J Med Chem 37 1233-1251, 1994. 

Applications of Combinatorial Technologies to Drug Discovery. 1. Background and Peptide Combinatorial Libraries. 

Amino Acids, Chemical Properties of Click Peptides, Design and Application of Peptide Combinatorial Libraries Solid-Phase Synthesis of Biomolecules... 

Array-Based Techniques for Glycans Development and Applications Peptide Combinatorial Libraries Transcript Profiling Receptor-Ligand Interactions... 

Solid phase attachment of histidine-containing peptides by anchoring the imidazole ring to trityl resins has been developed for combinatorial library preparation of diketopiperazines <99TL809>. Histidine, histamine, and urocanic acid are edl imidazole-containing molecules that have been attached to a trityl-type resin to allow their application to combinatorial chemistry <99TL2825>. 

What is discussed in this chapter is the situation of plant proteomics in terms of low-abundance proteins. Here is especially described a recent technology, along with dedicated applications, based on a unique sample treatment using combinatorial peptide ligand libraries (CPLL) that have already largely demonstrated their capabilities for novel discovery in animal protein science (2). The situation of both plant-derived food and drinks is reviewed throughout the context of plant proteomics. 

A special application of the peptide scan is the hybritope scan (hybrid-epitope) (44,45). In order to increase the affinity by extention of the peptide sequence in a hybritope scan, several mixtures of amino acids at positions flanking the related sequence of the protein are introduced. Another strategy to optimize a peptide scan is the so-called duotope scan (duo-epitope) (46). For a duotope scan one generates the peptide scan twice and combines the sequence of both arrays linked via a spacer, such as two -alanine molecules. In this way it is possible to avoid possible steric hindrance and to increase activity by extention of the active sequence. The pattern of such a duotope scan resembles that of a combinatorial library with the exception that each field represents a combination of two sequences rather than two amino acids. 

Schneider-Mergener, J., Kramer, A., and Reineke, U. (1996) Peptide libraries bound to continuous cellulose membranes tools to study molecular recognition. In Combinatorial Libraries Synthesis, Screening and Application Potential, ed. R. Cortese. New York Walter de Gruyter. 

A strategy of using different types of claims and claims of the same type but different in scope can be applied to robotics [2] used in making peptides and nucleotide sequences, libraries created on the surface of phage [9], diagnostics [10] which use combinatorial libraries or to virtually any invention in the field of molecular diversity - limitations on the type and scope of the claim being dictated by the prior art (under 35 USC 102 and 103 the claim cannot cover that which was previously known or claim subject matter deemed to be obvious in view of that which was previously known) existing at the time of the invention and the extent of disclosure included in the patent application. (A patent application must fully describe and disclose the invention which is claimed. This is referred to as an enablement requirement under 35 USC 112.)... 

Brummel CL, Vickerman JC, Carr SA, Hemling ME, Roberts GD, Johnson W, Weinstock J, Gaitanopoulos D, Benkovic SJ, Winograd N, Evaluation of mass spectrometric methods applicable to the direct analysis of non-peptide bead-bound combinatorial libraries, Anal. Chem., 68 237-242, 1996. 

Early reported applications of this technique were the preparation of a 24-member peptide library [83], of a 125-member tripeptide-substituted cinnamic acid library tested for inhibition of tyrosine phosphatase PTP1B [83], of a 64-member peptide-like library [83] and of libraries based on a natural product, epothilone, using also new polystyrene grafted solid supports [84], Other applications, ranging from l,5-benzodiazepin-2-one library synthesis [85] to chalcone library synthesis [86], were also recently reported. Commercialization of the basic components for this technique [87] (reaction supports and vessels, tags, software, sorters, reaction stations, and so on) will ensure its quick and effective use in combinatorial chemistry and also the implementation of new technical features and possibilities for more complex and demanding applications in future. 

---