Hormone sequence, biologically active

Many naturally occurring hormones and antibiotics are polypeptides and investigation into both the amino acid constituents and their sequence in the polypeptide chain are important areas of research. These investigations may reveal information regarding the biologically active part of the molecule, a fact that may then be used in the commercial production of a synthetic peptide... 

The ability to synthesize recombinant protein hormones has allowed greater access to treatment and the exploration of new uses for familiar hormones. The development of designer hormones represents the next step with alterations in amino-acid sequence resulting in changes in pharmacokinetics and differences in biological activity. 

What is most remarkable is that cells can produce proteins with strikingly different properties and activities by joining the same 20 amino acids in many different combinations and sequences. From these building blocks different organisms can make such widely diverse products as enzymes, hormones, antibodies, transporters, muscle fibers, the lens protein of the eye, feathers, spider webs, rhinoceros horn, milk proteins, antibiotics, mushroom poisons, and myriad other substances having distinct biological activities (Fig. 3-1). Among these protein products, the enzymes are the most varied and specialized. Virtually all cellular reactions are catalyzed by enzymes. 

The remaining prohormone contains stretches of amino acids sequences unrelated to biological activity. These sequences are removed by proteolytic enzymes such as endopeptidases which act on dibasic or monobasic amino acid residues, and exopeptidases (e.g., carboxypeptidases and aminopeptidases) which remove amino acid residues from the C-terminal and N-terminal ends, respectively. A single prohormone may yield one or more biologically active and distinct hormones. 

Leucine aminopeptidase (LAP, E.C.3.4.11.1) is one of the first discovered and the most widely studied aminopeptidase with respect to sequence, structure and mechanism of action.59 -63 LAP is a zinc containing exopeptidase that catalyzes the removal of amino acids from the N-terminus of peptides or proteins. Similar to other aminopeptidases, this enzyme is of significant biological and medical importance because of its key role in protein modification, activation, and degradation as well as in the metabolism of biologically active peptides and activity regulation of hormonal... 

The polymeric active ester method has been used successfully for the preparation of several small- to medium-sized peptides in very pure form the potentiality of the method has also been illustrated by the synthesis of a number of biologically active protein sequences like bradykinin 106), thyrotropin-releasing hormone 107), ACTH sequences 105), and LH—RH 108> in good overall yields. 

---