35115-62-9

Usage

InChI:InChI=1/C57H77N15O14/c1-3-30(2)47(56(84)71-22-8-14-42(71)55(83)72-23-9-15-43(72)57(85)86)68-49(77)36(16-18-44(58)73)64-51(79)40-12-6-21-70(40)54(82)39(25-32-28-60-29-62-32)67-52(80)41-13-7-20-69(41)53(81)38(24-31-27-61-34-11-5-4-10-33(31)34)66-50(78)37(26-45(59)74)65-48(76)35-17-19-46(75)63-35/h4-5,10-11,27-30,35-43,47,61H,3,6-9,12-26H2,1-2H3,(H2,58,73)(H2,59,74)(H,60,62)(H,63,75)(H,64,79)(H,65,76)(H,66,78)(H,67,80)(H,68,77)(H,85,86)/t30?,35?,36-,37-,38-,39-,40-,41-,42-,43-,47-/m0/s1

Upstream product

• 71989-31-6 Fmoc-Pro-OH 
• 71989-23-6 Fmoc-Ile-OH 
• 132388-59-1 L-Asn(Trt) 
• 109425-51-6 Fmoc-His(Trt)-OH 
• 143824-78-6 3-[(S)-2-carboxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)ethyl]indole-1-carboxylic acid tert-butyl ester 
• 98-79-3 L-Pyroglutamic acid 

Relevant academic research and scientific papers

Insights into cardiovascular effects of proline-rich oligopeptide (Bj-PRO-10c) revealed by structure-activity analyses: Dissociation of antihypertensive and bradycardic effects

We have previously reported that the proline-rich decapeptide from Bothrops jararaca (Bj-PRO-10c) causes potent and sustained antihypertensive and bradycardic effects in SHR. These activities are independent of ACE inhibition. In the present study, we used the Ala-scan approach to evaluate the importance of each amino acid within the sequence of Bj-PRO-10c (Pyr1-Asn 2-Trp3-Pro4-His5-Pro 6-Gln7-Ile8-Pro9-Pro10). The antihypertensive and bradycardic effects of the analogues Bj-PRO-10c Ala3, Bj-PRO-10c Ala7, Bj-PRO-10c Ala8 were similar to those of Bj-PRO-10c, whereas the analogues Bj-PRO-10c Ala 2, Bj-PRO-10c Ala4, Bj-PRO-10c Ala5, Bj-PRO-10c Ala9, and Bj-PRO-10c Ala10 kept the antihypertensive activity and lost bradycardic activity considerably. In contrast, Bj-PRO-10c Ala1 and Bj-PRO-10c Ala6 were unable to provoke any cardiovascular activity. In summary, we demonstrated that (1) the Pyr 1 and Pro6 residues are essential for both, the antihypertensive and bradycardic effects of Bj-PRO-10c; (2) Ala-scan approach allowed dissociating blood pressure reduction and bradycardic effects. Conformational properties of the peptides were examined by means of circular dichroism (CD) spectroscopy. The different Ala-scan analogues caused either an increase or decrease in the type II polyproline helix content compared to Bj-PRO-10c. The complete loss of activity of the Pro6 → Ala 6 mutant is probably due to the fact that in the parent peptide the His5-Pro6 bond can exist in the cis configuration, which could correspond to the conformation of this bond in the bound state. Current data support the Bj-PRO-10c as a promising leader prototype to develop new agents to treat cardiovascular diseases and its co-morbidities.