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Peptide-Drug Conjugate: Targeted Intracellular Drug Delivery by Molecular-Targeting Peptide

Research Project

Project/Area Number 18K14339
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 37010:Bio-related chemistry
Research InstitutionOsaka Prefecture University

Principal Investigator

Michigami Masataka  大阪府立大学, 理学(系)研究科(研究院), 助教 (60802428)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Keywordsドラッグデリバリーシステム / ペプチド-薬物複合体 / ヒト血管内皮増殖因子 / ドラッグデリバリー / ペプチド
Outline of Final Research Achievements

The aim of this study is to develop a molecular-targeting peptide that have high binding affinity like as antibodies. We have designed molecular-targeting peptides with a stable helix-loop-helix (HLH) structure as an alternatives to antibodies. Despite its low molecular weight, the HLH peptides exhibit high affinity and stability in serum (half-life: 14 days). As a new alternative to antibody-drug conjugates, we generated "ligand-targeting" peptide-drug conjugates, which utilize receptor-mediated endocytosis for targeted intracellular drug delivery. The peptide-drug conjugate makes a complex with an extracellular ligand and then binds to the receptor on the cell surface to stimulate intracellular uptake via the endocytotic pathway.

Academic Significance and Societal Importance of the Research Achievements

本基盤技術を確立できれば、他の標的タンパク質に対しても、自由自在にテーラーメイドの分子標的化合物が創出できる。すなわち、狙った細胞に任意の化合物を送達できるようになる。これを使って分子レベルで生命活動をコントロールすることで、従来の分子標的化合物では得ることのできなかった新しい知見を手に入れることが可能になる。また、本研究で開発する「ペプチド-薬物複合体」は、通常のペプチド固相合成による化学合成が可能であることから、細胞培養を基本とするバイオ医薬品の特殊な製造装置や、GMP管理を必要としないため、化学合成の設備しか持たない大学・企業でも、分子標的医薬の開発や製造への参入が可能となる。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (1 results)

All 2021

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results)

  • [Journal Article] A “ligand-targeting” peptide-drug conjugate: Targeted intracellular drug delivery by VEGF-binding helix-loop-helix peptides via receptor-mediated endocytosis2021

    • Author(s)
      Masataka Michigami, Kentaro Takahashi, Haruna Yamashita, Zhengmao Ye, Ikuhiko Nakase, Ikuo Fujii*
    • Journal Title

      PLoS One

      Volume: 16 Issue: 2 Pages: e0247045-e0247045

    • DOI

      10.1371/journal.pone.0247045

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access

URL: 

Published: 2018-04-23   Modified: 2023-01-30  

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