Peptide advances

NGR-TNF MolMed TNF fused to CNGRCG, a tumor vasculature-targeting (CD13) peptide Advanced solid tumors... 

During these discussions we have leaped forward many years in the history of peptide chemistry. We discussed the situation after the invention of the Z-group by Bergmann and Zervas in 1932 and the continuation of peptide research first in Dresden then in New York. There the analysis of amino acids and peptides advanced rapidly and this led to the present high-performance chromatographic method of Stein and Moore. At the same time, with the work of Fruton, a... 

Bricas, E. and Fromageot, Cl. (1953). Naturally occurring peptides, Advances in Protein Chemistry, 8, 1-25. 

Gupta, B., Levchenko, T. S. and Torchihn, V. P. (2005). Intracellular delivery of large molecules and small particles by cell-penetrating proteins and peptides. Advanced Drug Delivery Reviews, SI, 637-651. 

E. Bricas and C. Fromageot, Naturally occurring peptides, Advances in Protein Chem. 6,4 (1953). C. H. Li, Hormones of the anterior pituitary gland. Part I. Growth and adrenocorticotropic hormones. Advances in Protein Chem. 11, 102 (1956) Part II. Melanocyte-stimulating and lactogenic hormones. 12, 269 (1957). 

Harada, K., Fujii, K., Mayumi, T., Hibino, Y, and Suzuki, M., A method using LC/MS for determination of absolute configuration of constituent amino acids in peptide — Advanced Marfey s method. Tetrahedron Lett., 36, 1515, 1995. 

A major advance was devised by Pehr Edman (University of Lund Sweden) that has become the standard method for N terminal residue analysis The Edman degrada tion IS based on the chemistry shown m Figure 27 12 A peptide reacts with phenyl iso thiocyanate to give a phenylthwcarbamoyl (PTC) denvative as shown m the first step This PTC derivative is then treated with an acid m an anhydrous medium (Edman used mtromethane saturated with hydrogen chloride) to cleave the amide bond between the N terminal ammo acid and the remainder of the peptide No other peptide bonds are cleaved m this step as amide bond hydrolysis requires water When the PTC derivative IS treated with acid m an anhydrous medium the sulfur atom of the C=S unit acts as... 

The amount of sample required is quite small as little as 10 mole is typical So many peptides and proteins have been sequenced now that it is impossible to give an accurate count What was Nobel Prize winning work m 1958 is routine today Nor has the story ended Sequencing of nucleic acids has advanced so dramatically that it is possible to clone the gene that codes for a particular protein sequence its DNA and deduce the structure of the protein from the nucleotide sequence of the DNA We 11 have more to say about DNA sequencing m the next chapter... 

However, interpretation of, or even obtaining, the mass spectrum of a peptide can be difficult, and many techniques have been introduced to overcome such difficulties. These techniques include modifying the side chains in the peptide and protecting the N- and C-terminals by special groups. Despite many advances made by these approaches, it is not always easy to read the sequence from the mass spectrum because some amide bond cleavages are less easy than others and give little information. To overcome this problem, tandem mass spectrometry has been applied to this dry approach to peptide sequencing with considerable success. Further, electrospray ionization has been used to determine the molecular masses of proteins and peptides with unprecedented accuracy. 

Proteias, amino acids bonded through peptide linkages to form macromolecular biopolymers, used as chiral stationary phases for hplc iaclude bovine and human semm albumin, a -acid glycoproteia, ovomucoid, avidin, and ceUobiohydrolase. The bovine semm albumin column is marketed under the name Resolvosil and can be obtained from Phenomenex. The human semm albumin column can be obtained from Alltech Associates, Advanced Separation Technologies, Inc., and J. T. Baker. The a -acid glycoproteia and ceUobiohydrolase can be obtained from Advanced Separation Technologies, Inc. or J. T. Baker, Inc. 

The most recent advance in treating HIV infections has been to simultaneously attack the virus on a second front using a protease inhibitor. Recall from Section 27.10 that proteases are enzymes that catalyze the hydrolysis of proteins at specific points. When HIV uses a cell s DNA to synthesize its own proteins, the initial product is a long polypeptide that contains several different proteins joined together. To be useful, the individual proteins must be separated from the aggregate by protease-catalyzed hydrolysis of peptide bonds. Protease inhibitors prevent this hydrolysis and, in combination with reverse transcriptase inhibitors, slow the reproduction of HIV. Dramatic reductions in the viral load in HIV-infected patients have been achieved with this approach. 

Roberts, G. C. IC, and Jardetzky, O., 1970. Nuclear magnetic re.sonance. spectro.scopy of amino acids, peptides and proteins. Advances in Protein Chemistry 24 447-545. 

The development of peptides and proteins as therapeutic agents has been greatly accelerated by advances in the fields of biotechnology. 

This article summarises the general characteristics of a novel antibacterial target, peptide deformylase (PDF) and reviews the design, structure-activity relationships (SAR) and properties of known PDF inhibitors, including pre-clinical and clinical data for the most advanced members of this class. 

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