An Orally Active Bradykinin B₁ Receptor Antagonist Engineered as a Bifunctional Chimera of Sunflower Trypsin Inhibitor

Abstract

An orally active and metabolically stable peptide TIBA was successfully engineered as a chimera by fusing an analgesic bradykinin receptor antagonist peptide and the trypsin inhibitory loop of sunflower trypsin inhibitor-1. As a fusion cyclic peptide, the metabolically labile analgesic peptide is protected from degradation by exopeptidases as well as the endopeptidases, and its serum half-life extended from <5 min to >6 h as a chimera. Moreover, the chimera TIBA was also found to be orally active in an animal pain model using a hot plate assay.

Macrocyclic Antimicrobial Peptides Engineered from ω-Conotoxin

“…For preparing cyclic peptides by a thia-zip cyclization previously developed by our laboratory requires the design of a linear precursor with a cysteine at the N-terminus and a thioester at the C-terminus [3, 8, 22, 24-29]. Both Fmoc and Boc chemistry were employed for preparing the thioester precursors (Scheme 1A and 1B ) [24, 30, 31].…”

“…Successful examples include those guided by structures such as stapled peptides [4] and polycyclics [5] and those inspired by nature such as cyclic peptides [6] and lasso peptides [7]. In addition, recent examples have exploited the cyclic peptide scaffolds for drug design to obtain potent and orally-active bioactive peptides by inserting a bioactive peptide into an inter-cystine loop of a disulfide-rich cyclotide [3, 8]. …”

Молекулярные Аспекты Иммунитета Растений И Их Коэволюции С Насекомыми

“…Особенно интенсивно работают с ингибитором из подсолнечника в области медицины, где на его основе разрабатывают препараты для терапии опухолей, заболеваний крови, кожи, анальгетики и т. д. [9,29,30,61,102].…”

Linking inhibitor motions to proteolytic stability of sunflower trypsin inhibitor-1

“…[15][16][17][18][19][20] Sequences with completely novel function can be graed into the SFTI-1 framework, for engineering of radiopharmaceuticals, antimicrobials, proangiogenic compounds, and rheumatoid arthritis and autoimmune disease peptides. [21][22][23][24][25][26][27][28] SFTI-1 binds to trypsin in a substrate manner but can resist proteolysis for a quite long time. The hydrolysis rates of SFTI-1 and its analogs have been studied extensively.…”