Modified polypeptide compound with terminal side chain-tail chain linked to chiral diacid, and synthesis method thereof
A technology of peptide compound and synthesis method, which is applied in the field of chemical biology stable peptide methodology, can solve the problems of difficult prediction of the influence of peptide and target binding, cumbersome nitrogen alkylation module construction, and increased screening cost, so as to improve the peptide Good stability, sequence tolerance, and low cost effects
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Embodiment 1
[0081] Terminal D-aspartic acid modified polypeptide Ac-(cyclo-1,4)-[isoD-AspAlaAlaDapAlaAla]-NH 2 The synthesis of, namely the synthesis of structural formula (Ⅲ):
[0082]
[0083] The specific route is as follows:
[0084]
[0085] The specific operation steps are:
[0086] (1) Polypeptide solid-phase synthesis: Weigh 100 mg of Rinkamide MBHA resin in a 10 ml peptide tube, add 1 ml of N-methylpyrrolidone (NMP), swell the resin with nitrogen gas for 30 min, add 50% (v / v) morpholine NMP solution (v representative volume), blowing nitrogen for 30 min, NMP×5, dichloromethane (DCM)×5 alternately washed the resin 10 times in total. The prepared Fmoc-Ala-OH (5eq, 0.4M, NMP) solution, 6-chlorobenzotriazole-1,1,3,3-tetramethyluronium hexafluorophosphate (HCTU) (0.38M ,NMP) solution, N,N-diisopropylethylamine (DIPEA) according to 7.5:7.5:1 (v:v:v) after mixing, add nitrogen to the resin for 1h; take out the reaction solution, wash as above After the resin, proceed to the ne...
Embodiment 2
[0109] Terminally methylated L-type tartaric acid modified polypeptide (cyclo-1,4)-[L-tartaricacidAlaAlaDapAlaAla]-NH 2 The synthesis of, i.e. the synthesis of structural formula (Ⅳ):
[0110]
[0111] In Example 1, the chiral diacid was replaced with methylated L-type tartaric acid. The experimental procedure is the same as in Example 1, and the product can be directly obtained in step (5), without step (6). The final product can be obtained through high performance liquid chromatography purification, and the product is in H 2 Helicity increases in O (25°C). ( Figure 5 ,Table 2)
[0112] Table 2 Peptide IV at 25°C, H 2 Circular dichroism data in O
[0113]
[0114] The secondary structure of polypeptide α-helix is characterized by circular dichroism spectrum, which is characterized by a positive peak at 190nm, and a negative peak at 218nm (long peptide negative peak is at 222nm, and short peptide negative peak shifts), 208nm is negative peak and θ 218 / θ 208 ...
Embodiment 3
[0117] Terminal D-aspartic acid modified polypeptide Ac-(cyclo-1,4)-[isoD-AspValValDapAlaAla]-NH 2 The synthesis of, i.e. the synthesis of structural formula (Ⅴ):
[0118]
[0119] In Example 1, the amino acid sequence was replaced with two Val. Experimental procedure is identical with embodiment 1. After purification by high performance liquid chromatography, the final product can be obtained, and the stabilized polypeptide can be obtained in H 2 The characteristic α-helix in O (25°C) ( Figure 9 ,table 3).
[0120] Table 3 Polypeptide V at 25°C, H 2 Circular dichroism data in O
[0121]
[0122] The secondary structure of polypeptide α-helix is characterized by circular dichroism spectrum, which is characterized by a positive peak at 190nm, and a negative peak at 218nm (long peptide negative peak is at 222nm, and short peptide negative peak shifts), 208nm is negative peak and θ 218 / θ 208 The closer the ratio is to 1, the higher the helical content, and the ab...
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