Peptide diversity

An Evolutionary Model for Competence Stimulating Peptide Diversity 312... 

Addition of organometallic reagents to imines is not limited to allylmetal derivatives. Hoveyda and Snapper have demonstrated that dialkylzinc reagents can add to imines in a one-pot procedure. Using a zirconium complex as metal catalyst and a chiral peptide, diverse enantioenriched aryl, aliphatic and alkynyl amines 142 have been obtained with high levels of enantioselectivity (Scheme 8.60) [136],... 

SE Blondelle, E Perez-Paya, CT Dooley, C Pinilla, RA Houghten. Soluble combinatorial libraries of organic, peptidomimetic and peptide diversities. Trends Anal Chem 14 83-92, 1995. 

Blondelle, S. E., Perezpaya, E., Dooley, C. T., Pinilla, C. Houghten, R. A. (1995) Soluble Combinatorial Libraries of Organic, Peptidomimetic and Peptide Diversities. Trac-Trends in Analytical Chemistry 14, 83-92. 

Endogenous level of peptides (pmol/g tissue) Fig. 2.1 Concentration dependence on peptide diversity (estimate)... 

To understand the function of a protein at the molecular level, it is important to know its three-dimensional stmcture. The diversity in protein stmcture, as in many other macromolecules, results from the flexibiUty of rotation about single bonds between atoms. Each peptide unit is planar, ie, oJ = 180°, and has two rotational degrees of freedom, specified by the torsion angles ( ) and /, along the polypeptide backbone. The number of torsion angles associated with the side chains, R, varies from residue to residue. The allowed conformations of a protein are those that avoid atomic coUisions between nonbonded atoms. 

The primary cellular function of mRNA is to direct biosynthesis of the thousands of diverse peptides and proteins required by an organism—perhaps 100,000 in a human. The mechanics of protein biosynthesis take place on ribosomes, small granular particles in the cytoplasm of a cell that consist of about 60% ribosomal RNA and 40% protein. 

Because of their ease of synthesis and their structural similarity to peptides, many laboratories have used peptoids as the basis for combinatorial drug discovery. Peptoids were among the first non-natural compounds used to establish the basic principles and practical methods of combinatorial discovery [17]. Typically, diverse libraries of relatively short peptoids (< 10 residues) are synthesized by the mix-and-split method and then screened for biological activity. Individual active compounds can then be identified by iterative re-synthesis, sequencing of compounds on individual beads, or indirect deduction by the preparation of positional scanning libraries. 

With the aim of studying the formation of the 2.5-helix in water as well as to introduce side chain diversity, Gellman and his group synthesized / -peptides from a variety of / -amino acid building blocks (34-39) constrained with five-membered rings (Fig. 2.21). 

To obtain an increased intrinsic capacity to transgress biological membranes, a number of different modifications have been introduced to PNA. These modifications include conjugation of PNA to Hpophilic moieties [51, 97, 98], conjugation of PNA to certain so-caUed ceU-penetrating peptides [49, 55, 56, 66, 99-102] and conjugation to different moieties, which are supposed to be internahzed by specific cellular receptors [48, 103-105]. The work on cellular dehvery of PNA is, like the related work on ex vivo and in vivo effects of PNA, very difficult to summarize conclusively. First of all, the pronounced diversity of the reporter systems employed makes it impossible to directly compare the studies. Secondly, the widespread use of fluorescence studies in spite of the many inherent pitfalls of this technique makes it sometimes difficult to judge even qualitatively whether a presented result actually indicates cellular uptake. We have recently published a comprehensive review on cellular dehvery of PNA [82], with a more detailed assessment of the PNA dehvery hterature. 

Von Wintzingerode F., Landt O., Ehrlich A., Gobel U. B. Peptide nucleic acid-mediated PGR clamping as a useful supplement in the determination of microbial diversity. Appl. Environ. Microbiol. 2000 66 549-557. 

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