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Combinatorial libraries, peptide-based

Peptides and Peptidomimetics from Combinatorial Libraries. Mixture-based combinatorial peptide libraries have been extensively explored by Houghten and coworkers and have led to the identification of a variety of peptides with affinity for opioid receptors (see Ref 946 for a review). Early hexapeptide libraries, deconvoluted by binding to p opioid receptors and either iterative deconvolution (947)or positional scanning (948 see Ref 946 for a description of these deconvolution techniques), identified sequences related to the enkephalins. Other nonacetylated peptide libraries have identified more varied peptides, some that resemble opioid peptides and some that do not. Iterative deconvolution of a hexapeptide library resulted in identification of both Tyr-Pro-Phe-Gly-Phe-XNH, (X = one of 20 natural amino acids), reminiscent of the... [Pg.438]

Once binding hot spots are identified by DXMS analysis, combinatorial libraries can be generated, based in part on structural information available that may suggest the nature of the peptidic features of the interacting proteins that... [Pg.392]

Figure 3.5 Disulfide-based dynamic combinatorial library selects for peptidic tiomodi-sulfide P-P and acridone-peptide heterodisulfide A-P G-quadruplex DNA ligands. Figure 3.5 Disulfide-based dynamic combinatorial library selects for peptidic tiomodi-sulfide P-P and acridone-peptide heterodisulfide A-P G-quadruplex DNA ligands.
Another use for combinatorial libraries has been the screening of peptides for antimicrobrial properties. In this case, the design of the library is based on antimicrobial peptides found in nature. A combinatorial synthesis is used to find alternative unnatural amino acids expected to mimic the antimicrobial properties.23 Peptide libraries also have been used to find compounds that could bind the lytic peptide mellitin.24 The library was synthesized in solution phase, purified, and evaluated using time-of-flight mass spectrometry (TOF-MS). The sequences determined to bind to mellitin contained hydrophobic pairs. By binding to mellitin, they were able to prevent the cell-surface mellitin interaction. This is an example of a peptide library able to afford compounds that interact with other small peptides without having to find an interacting protein first. [Pg.292]

Mixture-Based Combinatorial Libraries From Peptides and Peptidomimetics to Small Molecule Acyclic and Heterocyclic Compounds... [Pg.496]

Many methods, merging peptide-chemistry with glycotechnology, have been improved, in order to introduce sugar moiety in peptide chain providing bases to create novel combinatorial libraries in automated or semi-automated... [Pg.35]

In collaboration with University of Trieste, we have developed rational approaches for the design and synthesis of peptidomimetic and non-peptidic inhibitors of HIV PR, utilizing structure-based [12-15], as well as combinatorial, library design methods [16, 17]. In this paper, we survey computer-assisted studies on the design, focusing and in silico screening of virtual combinatorial libraries of peptidomimetics and cyclic ureas, as potential anti-HIV agents, that were carried out in our laboratory. [Pg.57]


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