GALA peptide improves the potency of nanobody–drug conjugates by lipid-induced helix formation

2021 ◽  
Vol 57 (12) ◽  
pp. 1434-1437
Author(s):  
Ya Jie Chen ◽  
Qi Wen Deng ◽  
Li Wang ◽  
Xiao Chun Guo ◽  
Jian Yuan Yang ◽  
...  
Keyword(s):  
Membrane Binding ◽  
Drug Conjugates ◽  
Helix Formation ◽  
Drug Conjugation

We generated a potent nanobody–drug conjugation by fusing GALA, which forms helix induced by lipids, enhances membrane binding, and consequently increase cytotoxicity. We provides new insights into the GALA peptide and might boost the field of NDCs.

scholarly journals Influence of disulfide bond isoforms on drug conjugation sites in cysteine-linked IgG2 antibody-drug conjugates

mAbs ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 583-595 ◽  
Author(s):  
Lily Liu-Shin ◽  
Adam Fung ◽  
Arun Malhotra ◽  
Gayathri Ratnaswamy
Keyword(s):  
Disulfide Bond ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Drug Conjugation ◽  
Igg2 Antibody ◽  
Antibody Drug

Impact of Drug Conjugation on Pharmacokinetics and Tissue Distribution of Anti-STEAP1 Antibody–Drug Conjugates in Rats

2011 ◽  
Vol 22 (10) ◽  
pp. 1994-2004 ◽  
Author(s):  
C. Andrew Boswell ◽  
Eduardo E. Mundo ◽  
Crystal Zhang ◽  
Daniela Bumbaca ◽  
Nicole R. Valle ◽  
...  
Keyword(s):  
Tissue Distribution ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Drug Conjugation ◽  
Antibody Drug

Convergent synthesis of hydrophilic monomethyl dolastatin 10 based drug linkers for antibody–drug conjugation

2019 ◽  
Vol 17 (35) ◽  
pp. 8115-8124 ◽  
Author(s):  
Kanwen Yang ◽  
Bo Chen ◽  
Diego A. Gianolio ◽  
James E. Stefano ◽  
Michelle Busch ◽  
...  
Keyword(s):  
Convergent Synthesis ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Drug Conjugation ◽  
Hydrophilic Drug ◽  
Free Antibody ◽  
Antibody Drug ◽  
Dolastatin 10

A cytotoxic reagent-free fragment coupling methodology was developed to produce hydrophilic drug linkers to prepare aggregation free antibody–drug conjugates.

scholarly journals Recent Advances and Trends in Chemical CPP–Drug Conjugation Techniques

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1591
Author(s):  
Félix Gayraud ◽  
Merlin Klußmann ◽  
Ines Neundorf
Keyword(s):  
Cancer Cells ◽  
Organic Molecules ◽  
Cell Penetrating Peptide ◽  
Small Organic Molecules ◽  
Drug Conjugates ◽  
Drug Conjugation ◽  
Cell Penetrating ◽  
Recent Developments ◽  
Pros And Cons ◽  
Stimuli Sensitive

This review summarizes recent developments in conjugation techniques for the synthesis of cell-penetrating peptide (CPP)–drug conjugates targeting cancer cells. We will focus on small organic molecules as well as metal complexes that were used as cytostatic payloads. Moreover, two principle ways of coupling chemistry will be discussed direct conjugation as well as the use of bifunctional linkers. While direct conjugation of the drug to the CPP is still popular, the use of bifunctional linkers seems to gain increasing attention as it offers more advantages related to the linker chemistry. Thus, three main categories of linkers will be highlighted, forming either disulfide acid-sensitive or stimuli-sensitive bonds. All techniques will be thoroughly discussed by their pros and cons with the aim to help the reader in the choice of the optimal conjugation technique that might be used for the synthesis of a given CPP–drug conjugate

Interaction of a Mitochondrial Presequence with Lipid Membranes:  Role of Helix Formation for Membrane Binding and Perturbation†

Biochemistry ◽  
2000 ◽  
Vol 39 (50) ◽  
pp. 15297-15305 ◽  
Author(s):  
Torsten Wieprecht ◽  
Ognjan Apostolov ◽  
Michael Beyermann ◽  
Joachim Seelig
Keyword(s):  
Lipid Membranes ◽  
Membrane Binding ◽  
Helix Formation

scholarly journals Construction of homogeneous antibody–drug conjugates using site-selective protein chemistry

2016 ◽  
Vol 7 (5) ◽  
pp. 2954-2963 ◽  
Author(s):  
Padma Akkapeddi ◽  
Saara-Anne Azizi ◽  
Allyson M. Freedy ◽  
Pedro M. S. D. Cal ◽  
Pedro M. P. Gois ◽  
...  
Keyword(s):  
Therapeutic Efficacy ◽  
Protein Chemistry ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Drug Conjugation ◽  
Selective Chemical ◽  
Site Selective ◽  
Antibody Drug

The use of site-selective chemical drug-conjugation strategies enables the construction of antibody–drug conjugates (ADCs) with superior therapeutic efficacy.”

scholarly journals A Conjugate Based on Anti-HER2 Diaffibody and Auristatin E Targets HER2-Positive Cancer Cells

2017 ◽  
Vol 18 (2) ◽  
pp. 401 ◽  
Author(s):  
Anna Serwotka-Suszczak ◽  
Alicja Sochaj-Gregorczyk ◽  
Jerzy Pieczykolan ◽  
Daniel Krowarsch ◽  
Filip Jelen ◽  
...  
Keyword(s):  
Growth Factor Receptor ◽  
Drug Carriers ◽  
Her2 Positive ◽  
E Coli ◽  
Drug Conjugates ◽  
Drug Conjugation ◽  
Epidermal Growth ◽  
Intensive Investigation ◽  
Maleimide Group ◽  
Cell Analyzer

Antibody-drug conjugates (ADCs) have recently emerged as efficient and selective cancer treatment therapeutics. Currently, alternative forms of drug carriers that can replace monoclonal antibodies are under intensive investigation. Here, a cytotoxic conjugate of an anti-HER2 (Human Epidermal Growth Factor Receptor 2) diaffibody with monomethyl-auristatin E (MMAE) is proposed as a potential anticancer therapeutic. The anti-HER2 diaffibody was based on the ZHER2:4 affibody amino acid sequence. The anti-HER2 diaffibody has been expressed as a His-tagged protein in E. coli and purified by Ni-nitrilotriacetyl (Ni-NTA) agarose chromatography. The molecule was properly folded, and the high affinity and specificity of its interaction with HER2 was confirmed by surface plasmon resonance (SPR) and flow cytometry, respectively. The (ZHER2:4)2DCS-MMAE conjugate was obtained by coupling the maleimide group linked with MMAE to cysteines, which were introduced in a drug conjugation sequence (DCS). Cytotoxicity of the conjugate was evaluated using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide MTT assay and the xCELLigence Real-Time Cell Analyzer. Our experiments demonstrated that the conjugate delivered auristatin E specifically to HER2-positive tumor cells, which finally led to their death. These results indicate that the cytotoxic diaffibody conjugate is a highly potent molecule for the treatment of various types of cancer overexpressing HER2 receptors.

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