Convergent chemoenzymatic synthesis and biological evaluation of a heparan sulfate proteoglycan syndecan-1 mimetic.

A new convergent chemoenzymatic synthesis strategy, integrating enzymatic synthesis of heparan sulfate, sortase A ligation, copper(i)-catalyzed alkyne-azide cycloaddition, and solid phase peptide synthesis, has been established to efficiently synthesize a mimetic of heparan sulfate proteoglycan syndecan-1 glyco-polypeptide at a milligram scale. The mimic was able to bind with αvβ3 integrin faster and exhibit stronger inhibition of breast cancer cell migration compared to the glycan or the polypeptide alone. This novel approach could serve as a general approach for heparan sulfate proteoglycan mimetic synthesis.

• Publication year

  2021

• Venue

  Chemical Communications

• Publication date

  2021-03-09

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1039/d1cc00796cPMID 33687395PMCID PMC8052682
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Chemical synthesis of human syndecan-4 glycopeptide bearing O-, N-sulfation and multiple aspartic acids for probing impacts of the glycan chain and the core peptide on biological functions†

  2020cited by this paper
• Enhancing the efficiency of sortase-mediated ligations through nickel-peptide complex formation.

  2015cited by this paper
• Accelerated Fmoc solid-phase synthesis of peptides with aggregation-disrupting backbones.

  2015cited by this paper
• Homogeneous low-molecular-weight heparins with reversible anticoagulant activity.

  2014cited by this paper
• Docking Server for the Identification of Heparin Binding Sites on Proteins

  2014cited by this paper
• Chemical synthesis of syndecan-3 glycopeptides bearing two heparan sulfate glycan chains.

  2014cited by this paper
• PEP-SiteFinder: a tool for the blind identification of peptide binding sites on protein surfaces

  2014cited by this paper
• Heparin-protein interactions: from affinity and kinetics to biological roles. Application to an interaction network regulating angiogenesis.

  2014cited by this paper
• Chemical synthesis of a heparan sulfate glycopeptide: syndecan-1.

  2012cited by this paper
• A Systems Biology Approach for the Investigation of the Heparin/Heparan Sulfate Interactome*

  2011cited by this paper
• Architects at the bacterial surface — sortases and the assembly of pili with isopeptide bonds

  2011cited by this paper
• Heparan sulfate proteoglycans.

  2011cited by this paper
• Syndecan-1 couples the insulin-like growth factor-1 receptor to inside-out integrin activation

  2010cited by this paper
• Syndecan-1 regulates αvβ3 and αvβ5 integrin activation during angiogenesis and is blocked by synstatin, a novel peptide inhibitor

  2009cited by this paper
• Integrin signalling at a glance

  2009cited by this paper
• Molecular Interplay between Endostatin, Integrins, and Heparan Sulfate*

  2009cited by this paper
• Glypican-3 inhibits Hedgehog signaling during development by competing with patched for Hedgehog binding.

  2008cited by this paper
• Vesicles from peptidic side-chain polymers synthesized by atom transfer radical polymerization.

  2008cited by this paper
• Tumor alphavbeta3 integrin is a therapeutic target for breast cancer bone metastases.

  2007cited by this paper
• Tumor αvβ3 Integrin Is a Therapeutic Target for Breast Cancer Bone Metastases

  2007cited by this paper
• The function of a Drosophila glypican does not depend entirely on heparan sulfate modification.

  2006cited by this paper
• Sortase-mediated protein ligation: a new method for protein engineering.

  2004cited by this paper
• Heparin and Heparan Sulfate Biosynthesis

  2002cited by this paper

• Sortase-mediated labeling: Expanding frontiers in site-specific protein functionalization opens new research avenues.

  2024cites this paper
• The Role and Therapeutic Value of Syndecan-1 in Cancer Metastasis and Drug Resistance

  2022cites this paper
• Microreactor-based chemo-enzymatic ROP-ROMP platform for continuous flow synthesis of bottlebrush polymers

  2022cites this paper
• Chemical editing of proteoglycan architecture

  2022cites this paper
• Glycosaminoglycan Mimetic Precision Glycomacromolecules with Sequence-Defined Sulfation and Rigidity Patterns.

  2022cites this paper
• Polymers Inspired by Heparin and Heparan Sulfate for Viral Targeting

  2022cites this paper
• Excavating proteoglycan structure-function relationships: Modern approaches to capture the interactions of ancient biomolecules.

  2022cites this paper
• Precise Engineering of Lignin Incorporated Dextran/Glycol Nanomaterials for Wound Dressings for the Care of Anorectal Surgery

  2021cites this paper