Selective targeting of α7 nicotinic acetylcholine receptor by synthetic peptide mimicking loop I of human SLURP-1 provides efficient and prolonged therapy of epidermoid carcinoma in vivo

Shlepova, O. V.; Shulepko, M. A.; Shipunova, V. O.; Bychkov, M. L.; Kukushkin, I. D.; Chulina, I. A.; Azev, V. N.; Shramova, E. I.; Kazakov, V. A.; Ismailova, A. M.; Palikova, Y. A.; Palikov, V. A.; Kalabina, E. A.; Shaykhutdinova, E. A.; Slashcheva, G. A.; Tukhovskaya, E. A.; Dyachenko, I. A.; Murashev, A. N.; Deyev, S. M.; Kirpichnikov, M. P.; Shenkarev, Z. O.; Lyukmanova, E. N.

doi:10.3389/fcell.2023.1256716

Cited by 6 publications

(1 citation statement)

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“…Possible applications may lie in their synthetic peptide fragments as was shown for a peptide fragment of Lynx1, which preserved the spatial structure of the Lynx1 central loop II and bound to the T. californica nAChR as efficiently as ws-Lynx1 itself [40]. Intravenous injection of a synthetic peptide mimicking SLURP-1's loop I (Oncotag) suppressed tumor growth and metastasis in a xenograft mice model of epidermoid carcinoma in a similar way to rSLURP-1 [41].…”

Section: Discussionmentioning

confidence: 99%

Comparison of Conformations and Interactions with Nicotinic Acetylcholine Receptors for E. coli-Produced and Synthetic Three-Finger Protein SLURP-1

Kost,

Sukhov,

Ivanov

et al. 2023

IJMS

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SLURP-1 is a three-finger human protein targeting nicotinic acetylcholine receptors (nAChRs). The recombinant forms of SLURP-1 produced in E. coli differ in added fusion fragments and in activity. The closest in sequence to the naturally occurring SLURP-1 is the recombinant rSLURP-1, differing by only one additional N-terminal Met residue. sSLURP-1 can be prepared by peptide synthesis and its amino acid sequence is identical to that of the natural protein. In view of recent NMR analysis of the conformational mobility of rSLURP-1 and cryo-electron microscopy structures of complexes of α-bungarotoxin (a three-finger snake venom protein) with Torpedo californica and α7 nAChRs, we compared conformations of sSLURP-1 and rSLURP-1 by Raman spectroscopy and CD-controlled thermal denaturation, analyzed their competition with α-bungarotoxin for binding to the above-mentioned nAChRs, compared the respective receptor complexes with computer modeling and compared their inhibitory potency on the α9α10 nAChR. The CD revealed a higher thermostability of sSLURP-1; some differences between sSLURP-1 and rSLURP-1 were observed in the regions of disulfides and tyrosine residues by Raman spectroscopy, but in binding, computer modeling and electrophysiology, the proteins were similar. Thus, sSLURP-1 and rSLURP-1 with only one additional Met residue appear close in structure and functional characteristics, being appropriate for research on nAChRs.

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Section: Discussionmentioning

confidence: 99%