Polypeptide Elaboration

GH is a 191-residue polypeptide elaborated by the anterior pituitary. The amino acid sequence of GH has been determined, and comparison with growth hormone.s of different species has revealed considerable structural variation. In addition, the structure and properties of human GH have been reviewed. "... 

Figure 2.11 Beta sheets are usuaiiy represented simply by arrows in topology diagrams that show both the direction of each (3 strand and the way the strands are connected to each other along the polypeptide chain. Such topology diagrams are here compared with more elaborate schematic diagrams for different types of (3 sheets, (a) Four strands. Antiparallel (3 sheet in one domain of the enzyme aspartate transcarbamoylase. The structure of this enzyme has been determined to 2.8 A resolution in the laboratory of William Lipscomb, Harvard University, (b) Five strands. Parallel (3 sheet in the redox protein flavodoxin, the structure of which has been determined to 1.8 A resolution in the laboratory of Martha Ludwig, University of Michigan, (c) Eight strands. Antiparallel barrel in the electron carrier plastocyanln. This Is a closed barrel where the sheet is folded such that (3 strands 2 and 8 are adjacent. The structure has been determined to 1.6 A resolution in the laboratory of Hans Freeman in Sydney, Australia. (Adapted from J. Richardson.)...

While the a-helix of L-a-peptides and the (M)-3i4 helix of the corresponding peptides have opposite polarity and helicity (see Section 2.2.3.1), the inserhon of two CH2 groups in the backbone of L-a-amino acids leave these two hehx parameters unchanged, both the a-helix and the 2.614-hehx of the resulting y" -peptides being right-handed and polarized from N to C terminus. In view of these similarities, the y-peptide hehcal fold might prove useful as a template to elaborate functional mimetics of bioachve a-polypeptides. 

The inherent drawbacks of the oxidative refolding approach for synthetic polypeptides containing multiple cysteine residues is the individual behavior of each peptide that derives from the encoded sequence, more or less pronounced structural information which prevents general procedures to be elaborated and proposed. Nevertheless, this synthetic approach remains attractive because of its simplicity compared to the synthetic strategies for re-gioselective disulfide bond formation (Section 6.1.1-6.1.4), and it is certainly indispensable if the number of cysteine residues exceeds the presently available chemistry for site-directed cysteine pairings. 

The chemical polycondensation method has as yet been elaborated only for polymers with 1,2-trans-glycosidic linkages between the repeating units, but within these limits it seems to be a rather broad chemical method. It is the first purely chemical method for the synthesis of complex polysaccharides, as was demonstrated before for polypeptides and polynucleotides. ... 

It is important to stress from the outset that these metal complexes do not aim to model the complicated polypeptide environment of the active site in the enzyme but are designed to keep the system as simple as possible so that the chemistry associated with binding and activation of N2 can be defined in detail. The study on N2 complexes does not elaborate just the pathway that the enzyme adopts to convert N2 to NH3, but a wide variety of conceivable routes that are available. The role of the chemist is in part to delineate all of the possible pathways by which N2 can be converted through to NH3. It is just as important to understand the pathways that the enzyme does not use as it is to know the route it does adopt if we are to appreciate fully the mechanism of the nitrogenases. 

Many of the present controlled release devices for in vivo delivery of macromo-lecular drugs involve elaborate preparation, often employing either harsh chemicals,such as organic solvents [171] or extreme conditions, such as elevated temperature [172]. The conditions have the potential to destroy the activity of sensitive macromolecular drugs, such as proteins or polypeptides. In addition, many devices require surgical implantation and, in some cases, the matrix remains behind or must be surgically removed after the drug is exhausted [173]. 

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