Wolfgang Dr. König

Amine Protecting Groups

Publisher Summary This chapter provides an overview of amine protecting groups. A main guideline for principles concerning the selection of protecting group is the cleavage condition to which a given peptides proved to be sufficiently stable. Because of the stability of a great number of peptides and proteins against acidolysis in aqueous or anhydrous medium, much attention has been devoted to acid-labile protecting groups of the urethane type. Thus, highly differentiated acid lability becomes the most frequently employed principle of cleavage, complemented by hydrogenation and, more recently, by β-elimination. The favorable properties of the 9-fluorenylmethyloxycarbonyl group led to a novel strategy to use this residue for Nα protection and tert-butyl-type groups for side-chain protection in solid-phase synthesis.

New analogues of secretin.

For the evaluation of structure/activity relationships, some porcine secretin analogues, modified in the N-terminus, have been synthesized by segment condensation in solution. The secretin activity of the analogues was defined as the volume of pancreatic juice secreted in rats and dogs. The exchange of the N-terminal pentapeptide for the N-terminal pentapeptide of human somatotropin releasing factor (h-SRF) resulted in a peptide ([1-Tyr,2,4-Di-Ala,5-Ile]secretin) with practically no SRF-activity (less than 1% SRF-activity up to 100 micrograms/kg in the rat), but surprisingly high secretin activity (almost 100% in the rat, but only 1150 CU/mg (27%) in the dog). [3-L-Cysteic acid]secretin showed 1750 CU/mg (39%) in the dog, but a less activity (23%) in the rat. [6-D-Phe]secretin and [5-D-allo-Thr]secretin are again strongly species specific. They exhibited an activity of less than 1% in the dog, but about 10-15% in the rat. The smallest secretin activity was observed with [1-Cys,6-Cys]secretin in the oxidized form. The activity in the rat with this analogue was only about 0.2%.

Synthese eines Triacontatripeptids der Sequenz 31-63 des Schweine-Proinsulins

The synthesis of the sequence 31 — 63 of the porcine proinsulin connecting the B- and A-chain is described.

Analogues and fragments of secretin

For the purpose of analytical investigation and structure/activity relationships, some secretin analogues and secretin fragments have been synthesized. HPLC comparison of the synthesized products with our synthetic secretin revealed about 2% [D-Ala17]secretin, 1% [D-Leu13]secretin and less than 1% aminoterminal degradation products. The D-Ala17 content can be eliminated if the starting material used for segment coupling (Z-Arg(Z2)-Asp(OBut)-Ser(But)-Ala-OH) has no D-Ala-contamination. In addition, traces of the rearrangement products [3-aspartoyl]-secretin and [beta-Asp3]secretin are suspected. Secretin can be degraded to several compounds by chromatography on a strong basic ion exchanger in 1% acetic acid. These products are more polar than secretin and have no biological activity. The secretin content measured by HPLC correlated well with the biological data, since the degradation products and other byproducts separated by HPLC have only a negligible influence on the pancreatic flow.