The C‐Terminal Heptapeptides of Suzukacillin A and Alamethicin F30 — Sequence, Conformation, and Synthesis

Abstract

Suzukacillin A is a potential-dependent membrane pore-forming polypeptide antibiotic exhibiting similar properties as alamethicin in biophysical1.2) and biological3-6) experiments. The essential a-helical part of these polypeptides with its high dipole moment is responsible for potential-dependent pore formation in black lipid membranes as described by the flip-flop gating model7). On the other hand the polarity and size of the C-and N-termini determine specific characteristics such as medium pore size and stability of pore statesa.9). Thus the exact knowledge of structure/activity relations contributes considerably to a better understanding of the ionconduction properties of these linear amphiphilic polypeptides.A preliminary sequence based solely on GC-MS studies of partial fragments was published 1976 by our groups'). As alamethicin'O.'') and trichotoxin A40'2-'4) the eicosapeptide suzukacillin A belongs to the longest peptide antibiotics known and shows a characteristic natural microheterogeneity in its amino acid composition. Because of several ambiguities in the former instrumental sequencing') it was necessary to isolate and 0 VCH Verlagsgesellschaft mbH, D-6940 Weinheim, 1985

The chemistry of peptides related to metabolites of Trichoderma spp. 2. An improved method of characterization of peptides of 2-methylalanine

“…1 l), the suzukacillins (6), and the alamethicins (12) are very complex mixtures and that the proportions of the individual components of the mixture depend on the conditions of growth of the producing fungus. These facts and the worldwide interest in the physiological properties of these materials have led to extraordinary synthetic efforts to obtain a single entity by synthesis (13)(14)(15)(16)(17). The results of these efforts in the alamethicin field have been symmarized by Schmidt and Jung (16), who show that the measurements of the physical properties of the synthetic products by the different groups fall outside normally accepted ranges of error.…”

Peptaibiomics: Towards a Myriad of Bioactive Peptides Containing Cα‐Dialkylamino Acids?

“…In this context, the previously established presence of d-Iva [59] was confirmed. However, both l-Val/dIva and l-Leu/l-Ile were detected in HCl hydrolysates of SZ-A by chiral GC/MS, thus increasing the previously established sequence combinations for the main C-terminal heptapeptides of SZ-A [184]. However, it appears as if the suzukacillin-producing strain is no longer deposited, -neither in industrial, nor in public culture collections.…”

Anwendung der Azirin/Oxazolon‐Methode in der Peptid‐Chemie: Synthese von Modell‐Tripeptiden

“…IR (CHCI,): 3430w, 3005w, 2965m, 2935w, 2875w, 1716m, 1682s, 1643~1, 1596~1, 14963, 1454~1, 1372m, 1343w, 1233w, 1125w, 1089w, 1044w, 1028w. 'H-NMR (200 MHz, CDCI,): 7,4-7,05 (m, 10 ',4 MHz,CDCI,): 171,9,169,s (2s,155,9 (s,144,5,136,4,129,4,128,5,128,1,128,0,127,5,127,2 (12 arom. C): 67,s (s, C(2.2)); 66,8 (t. PhCH20); 59,O (d, C(2.1)); 40,s (4.…”

“…H); 6,86(s, NH); 6,6 (hr., COOH); 5,64 (d, J = 8, NH); 5,lO (s, PhCH20); 4,03 (dd, J = 8, 7, CH(2.1)); 2,35-1,0 (m, CH3(3.1), CH2(4.1), 8 H von Acp); 0,92 (d, J = 7, CH3(3'.1)); 0 3 8 (I, J = 7,CH,(5.1)). "C-NMR (50,4 MHz, CDC1,): 176,9 (s, COOH); 172,l (s, Amid-CO); 156,7 (s, Urethan-CO); 136, 1,128,5,128,1,127,9 (6arom. C);67,l ( t ,PhCH,O); 66,2 (s, C(2.2)); 59,5 (d, C(Z.1)); 37,2(d,C(3.1)); 37, 1,36,8(2t, C(3.2), C(6.2)); 24,7,24,53,24,50(3t,C(4.I),C(4.2), C(5.2)); 15,3 (4, C(3I.I)); 11,l (q, C(5.1)).…”