A structurally minimized yet fully active insulin based on cone-snail venom insulin principles

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Standard

A structurally minimized yet fully active insulin based on cone-snail venom insulin principles. / Xiong, Xiaochun; Menting, John G.; Disotuar, Maria M.; Smith, Nicholas A.; Delaine, Carlie A.; Ghabash, Gabrielle; Agrawal, Rahul; Wang, Xiaomin; He, Xiao; Fisher, Simon J.; MacRaild, Christopher A.; Norton, Raymond S.; Gajewiak, Joanna; Forbes, Briony E.; Smith, Brian J.; Safavi-Hemami, Helena; Olivera, Baldomero; Lawrence, Michael C.; Chou, Danny Hung Chieh.

I: Nature Structural and Molecular Biology, Bind 27, 2020, s. 615-624.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Xiong, X, Menting, JG, Disotuar, MM, Smith, NA, Delaine, CA, Ghabash, G, Agrawal, R, Wang, X, He, X, Fisher, SJ, MacRaild, CA, Norton, RS, Gajewiak, J, Forbes, BE, Smith, BJ, Safavi-Hemami, H, Olivera, B, Lawrence, MC & Chou, DHC 2020, 'A structurally minimized yet fully active insulin based on cone-snail venom insulin principles', Nature Structural and Molecular Biology, bind 27, s. 615-624. https://doi.org/10.1038/s41594-020-0430-8

APA

Xiong, X., Menting, J. G., Disotuar, M. M., Smith, N. A., Delaine, C. A., Ghabash, G., Agrawal, R., Wang, X., He, X., Fisher, S. J., MacRaild, C. A., Norton, R. S., Gajewiak, J., Forbes, B. E., Smith, B. J., Safavi-Hemami, H., Olivera, B., Lawrence, M. C., & Chou, D. H. C. (2020). A structurally minimized yet fully active insulin based on cone-snail venom insulin principles. Nature Structural and Molecular Biology, 27, 615-624. https://doi.org/10.1038/s41594-020-0430-8

Vancouver

Xiong X, Menting JG, Disotuar MM, Smith NA, Delaine CA, Ghabash G o.a. A structurally minimized yet fully active insulin based on cone-snail venom insulin principles. Nature Structural and Molecular Biology. 2020;27:615-624. https://doi.org/10.1038/s41594-020-0430-8

Author

Xiong, Xiaochun ; Menting, John G. ; Disotuar, Maria M. ; Smith, Nicholas A. ; Delaine, Carlie A. ; Ghabash, Gabrielle ; Agrawal, Rahul ; Wang, Xiaomin ; He, Xiao ; Fisher, Simon J. ; MacRaild, Christopher A. ; Norton, Raymond S. ; Gajewiak, Joanna ; Forbes, Briony E. ; Smith, Brian J. ; Safavi-Hemami, Helena ; Olivera, Baldomero ; Lawrence, Michael C. ; Chou, Danny Hung Chieh. / A structurally minimized yet fully active insulin based on cone-snail venom insulin principles. I: Nature Structural and Molecular Biology. 2020 ; Bind 27. s. 615-624.

Bibtex

@article{10a0e5fed1b64551a223915ba0577872,
title = "A structurally minimized yet fully active insulin based on cone-snail venom insulin principles",
abstract = "Human insulin and its current therapeutic analogs all show propensity, albeit varyingly, to self-associate into dimers and hexamers, which delays their onset of action and makes blood glucose management difficult for people with diabetes. Recently, we described a monomeric, insulin-like peptide in cone-snail venom with moderate human insulin-like bioactivity. Here, with insights from structural biology studies, we report the development of mini-Ins—a human des-octapeptide insulin analog—as a structurally minimal, full-potency insulin. Mini-Ins is monomeric and, despite the lack of the canonical B-chain C-terminal octapeptide, has similar receptor binding affinity to human insulin. Four mutations compensate for the lack of contacts normally made by the octapeptide. Mini-Ins also has similar in vitro insulin signaling and in vivo bioactivities to human insulin. The full bioactivity of mini-Ins demonstrates the dispensability of the PheB24–PheB25–TyrB26 aromatic triplet and opens a new direction for therapeutic insulin development.",
author = "Xiaochun Xiong and Menting, {John G.} and Disotuar, {Maria M.} and Smith, {Nicholas A.} and Delaine, {Carlie A.} and Gabrielle Ghabash and Rahul Agrawal and Xiaomin Wang and Xiao He and Fisher, {Simon J.} and MacRaild, {Christopher A.} and Norton, {Raymond S.} and Joanna Gajewiak and Forbes, {Briony E.} and Smith, {Brian J.} and Helena Safavi-Hemami and Baldomero Olivera and Lawrence, {Michael C.} and Chou, {Danny Hung Chieh}",
note = "Author Correction: https://www.nature.com/articles/s41594-020-0460-2",
year = "2020",
doi = "10.1038/s41594-020-0430-8",
language = "English",
volume = "27",
pages = "615--624",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - A structurally minimized yet fully active insulin based on cone-snail venom insulin principles

AU - Xiong, Xiaochun

AU - Menting, John G.

AU - Disotuar, Maria M.

AU - Smith, Nicholas A.

AU - Delaine, Carlie A.

AU - Ghabash, Gabrielle

AU - Agrawal, Rahul

AU - Wang, Xiaomin

AU - He, Xiao

AU - Fisher, Simon J.

AU - MacRaild, Christopher A.

AU - Norton, Raymond S.

AU - Gajewiak, Joanna

AU - Forbes, Briony E.

AU - Smith, Brian J.

AU - Safavi-Hemami, Helena

AU - Olivera, Baldomero

AU - Lawrence, Michael C.

AU - Chou, Danny Hung Chieh

N1 - Author Correction: https://www.nature.com/articles/s41594-020-0460-2

PY - 2020

Y1 - 2020

N2 - Human insulin and its current therapeutic analogs all show propensity, albeit varyingly, to self-associate into dimers and hexamers, which delays their onset of action and makes blood glucose management difficult for people with diabetes. Recently, we described a monomeric, insulin-like peptide in cone-snail venom with moderate human insulin-like bioactivity. Here, with insights from structural biology studies, we report the development of mini-Ins—a human des-octapeptide insulin analog—as a structurally minimal, full-potency insulin. Mini-Ins is monomeric and, despite the lack of the canonical B-chain C-terminal octapeptide, has similar receptor binding affinity to human insulin. Four mutations compensate for the lack of contacts normally made by the octapeptide. Mini-Ins also has similar in vitro insulin signaling and in vivo bioactivities to human insulin. The full bioactivity of mini-Ins demonstrates the dispensability of the PheB24–PheB25–TyrB26 aromatic triplet and opens a new direction for therapeutic insulin development.

AB - Human insulin and its current therapeutic analogs all show propensity, albeit varyingly, to self-associate into dimers and hexamers, which delays their onset of action and makes blood glucose management difficult for people with diabetes. Recently, we described a monomeric, insulin-like peptide in cone-snail venom with moderate human insulin-like bioactivity. Here, with insights from structural biology studies, we report the development of mini-Ins—a human des-octapeptide insulin analog—as a structurally minimal, full-potency insulin. Mini-Ins is monomeric and, despite the lack of the canonical B-chain C-terminal octapeptide, has similar receptor binding affinity to human insulin. Four mutations compensate for the lack of contacts normally made by the octapeptide. Mini-Ins also has similar in vitro insulin signaling and in vivo bioactivities to human insulin. The full bioactivity of mini-Ins demonstrates the dispensability of the PheB24–PheB25–TyrB26 aromatic triplet and opens a new direction for therapeutic insulin development.

U2 - 10.1038/s41594-020-0430-8

DO - 10.1038/s41594-020-0430-8

M3 - Journal article

C2 - 32483339

AN - SCOPUS:85085878153

VL - 27

SP - 615

EP - 624

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

SN - 1545-9993

ER -

ID: 244531737