Patent ID: 6274551
Filing Date: 2001-08-14
Classification: A61K,A61P,C07K

Abstract:
A substially pure compound Kahalalide F, said compound hag a molecular formula of C.sub.75 H.sub.124 N.sub.14 O.sub.16, and consisting of five valines, two isoleucines, two threonines, ornithine, dehydroaminobutynic acid, proline, phenylalanine and 5-methylhexanoic acid; said compound further exhibiting the following physical and chemical properties: [.alpha.].sub.D -8.degree. (c 4.32, MeOH; .sup.1 H NMR (500 MHz, TFA/DMF); amino acid unit, .delta. (carbon position, mult, J): Val-1 4.16 (2, t, J=9.0 Hz), 7.11 (NH on 2, d, J=8,9 Hz), 1.77 (3, m), 0.95 (4, m), 0.95(5, m), Dhb 9.20 (NH on 2, s), 6.48 (3, q, J=6.9 Hz), 1.43 (4, d, J=6.6 Hz); Phe 4.68 (2, q, J=6.6 Hz), 8.62 (NH on 2, d, J=6.6 Hz), 3.2 (3, dd, J=13.7, 7.2 Hz), 3.0 (3, dd, J=13.7, 9.0 Hz), 7.32 (5, d, J=7.2 Hz), 7.28 (6, t J=7.5 Hz), 7.21 (7, t, J=7.2 Hz); Vol-2 4.36 (2, m), 7.82 (NH on 2, d, J=6.6 Hz), 2.12 (3, m), 0.85 (4, m), 0.77 (5, d, J=6.6 Hz); Ileu-1 4.53 (2, m), 8.38 (NH on 2, d, J=9.6 Hz), 1.98 (3, m), 0.92 (4, d, J=6.6 Hz), 1.40 (5, m), 1.13 (5, m), 0.88 (6, t, J=7.2 Hz); Thr-1 4.63 (2, t, J=9.3 Hz), 8.12 (HN on 2, d, J=5.7), 5.07 (3, dq, 9.6, 6.0 Hz), 1.18 (4, d, J=6.3 Hz); Ilue-2 4.52 (2, m), 7.72 NH on 2, d, J=8.4 Hz), 1.88 (3, m), 0.88 (4, d, J-6.3 Hz), 1.40 (5, m) 1.13 (5, m), 0.88 (6d, J=7.2 Hz) Orn 4.48 (2, m), 7.92 (NH on 2, d, J=7.8 Hz), 1.76 (3, m), 1.83 (4, m), 3.10 (5, p, J=5.1 Hz); Pro 4.42 (2, m), 2.12 (3, m), 1.97 (3, m), 2.02 (4, m), 1.88 (4, m), 3.75 (5, m), 3.68 (5, m); Val-3 4.41 (2, m), 7.90 (NH on 2, d, J=7.2 Hz), 2.12 (3, m), 0.95 (4, m), 0.85 (5, m); Val-4 4.34 (2, m), 7.68 (NH on 2, d, J=8.1 Hz), 2.17 (3, m), 0.95 (4, m), 0.90 (5, m); Thr-2 4.46 (2, m), 7.77 (NH on 2, d, J=8.1Hz), 4.21 (3, dq, 6.3, 3.6 Hz), 1.12 (4, d, J=6.6 Hz); Val-5 4.32 (2, m), 7.85, (HN on 2, d, J=8.1 Hz), 7.82 (NH on (second conformation), d, J=8.1 Hz), 2.14 (3, m), 0.95(4, m), 0.90 (5, m); 5-MeHex 2.26 (2, m), 1.60 (3, m), 1.20 (4, m), 1.55 (5, m), 0.87 (6, d, J=7.2 Hz), 0.87 (7, d, J=72 Hz); 5-MeHex 2.29 (2, m), 1.65 (3, m), 1.40 (3, m), 1.13 (4, m),1.35 (5, m), 0.90 (6, m), 0.90 (7, m); .sup.13 C NMR (125 MHz TFA/DMF): amino acid unit, .delta. (carbon position); Val-1 170.40 (1), 60.31 (2), 30.75 (3), 19.58 (4), 18.76 (5); Dhb 164.54 (1), 130.30 (2), 131.26 (3), 126.6 (4); Phe 171.31 (1), 56.27 (2), 36.79 (3), 138.23 (4), 129.86 (5), 128.77 (6), 126.98 (7); Val-2 172.94 (1), 58.57 (2), 32.38 (3), 18.92 (4), 17.60 (5);Ileu-1 171.87 (1), 57.48 (2), 38.78 (3), 14.56 (4), 26.78 (5), 11.67; Thr-1 169.68 (1), 57.37 (2), 71.05 (3), 17.34 (4); Ileu-2 171.92 (1), 57.29 (2), 38.01 (3), 14.78 (4), 26.55 (5), 11.63 (6); Orn 172.01 (1), 52.87 (2), 29.63 (3), 24.39 (4), 40.05 (5); Pro 172.55 (1), 60.23 (2), 29.58 (3), 25.38 (4), 48.03 (5); Val-3 171.28 (1), 57.57 (2), 30.54 (3), 19.61 (4), 18.80 (5); Val-4 171.83 (1), 59.10 (2), 31.26 (3), 19.45 (4), 18.08 (5); thr-2 170.97 (1), 58.89 (2), 67.36 (3), 19.66 (4); Val-5 172.67 (1), 59.64 (2), 30.66 (3), 19.61 (4), 18.43 (5); 5-MeHex 173.83 (1), 36.28 (2), 23.99 (3), 38.96 (4), 28.10 (5), 22.54 (6), 22.50 (7); 5-MeHex (second conformation) 174.08 (1), 33.86 (2), 32.84 (3), 29.75 (4), 34.54 (5), 19.51 (6), 11.20 (7); IR neat (NaCl): 3287 (s, br), 2964 (s, br), 1646 (s), 1528 (s), 1464 (s), 1388 (m), 1228 (m), cm.sup.-1 ; mass spectrum HRFAB m/z (fragment, %) 1477.9408 (M.sup.+ +1, 85); UV (MeOH): .lambda..sub.max 204 (89,630) nm.