Glycan Modulation of Insulin‐like Growth Factor‐1 Receptor

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Abstract: The insulin‐like growth factor‐1 receptor (IGF‐1R) is a receptor tyrosine kinase (RTK) that plays critical roles in cancer. Microarray, computational, thermodynamic, and cellular imaging studies reveal that activation of IGF‐1R by its cognate ligand IGF1 is inhibited by shorter, soluble heparan sulfate (HS) sequences (e.g., HS06), whereas longer polymeric chains do not inhibit the RTK, a phenomenon directly opposed to the traditional relationship known for GAG‐protein systems. The inhibition arises from smaller oligosaccharides binding in a unique pocket in the IGF‐1R ectodomain, which competes with the natural cognate ligand IGF1. This work presents a highly interesting observation on preferential and competing inhibition of IGF‐1R by smaller sequences, whereas polysaccharides are devoid of this function. These insights will be of major value to glycobiologists and anti‐cancer drug discoverers.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
Glycan Modulation of Insulin‐like Growth Factor‐1 Receptor ; day:09 ; month:11 ; year:2022 ; extent:1
Angewandte Chemie / International edition. International edition ; (09.11.2022) (gesamt 1)

Urheber
Boothello, Rio S.
Sankaranarayanan, Nehru Viji
Sistla, Jyothi C.
Nagarajan, Balaji
Sharon, Chetna
Chittum, John E.
Niyaz, Rabiya Y.
Roy, Swarnali
Nandi, Aditi
O'Hara, Connor P.
Gangji, Rahaman Navaz
Afosah, Daniel K.
Ongolu, Ravikumar
Patel, Bhaumik B.
Desai, Umesh R.

DOI
10.1002/anie.202211320
URN
urn:nbn:de:101:1-2022111014250807804855
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
15.08.2025, 07:28 MESZ

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Beteiligte

  • Boothello, Rio S.
  • Sankaranarayanan, Nehru Viji
  • Sistla, Jyothi C.
  • Nagarajan, Balaji
  • Sharon, Chetna
  • Chittum, John E.
  • Niyaz, Rabiya Y.
  • Roy, Swarnali
  • Nandi, Aditi
  • O'Hara, Connor P.
  • Gangji, Rahaman Navaz
  • Afosah, Daniel K.
  • Ongolu, Ravikumar
  • Patel, Bhaumik B.
  • Desai, Umesh R.

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