松田豊（Yutaka Matsuda)-ADC Chemist-
@matsudaphdphd.bsky.social
Posting about antibody-drug conjugates (ADC), biopharma, and organic synthesis. I'm an ADC Chemistry Director in a U.S. pharma company, with a background in AJICAP and Exo-linker development, two Ph.D.s, and an MBA. Views are my own.
7. AG Mutation:
A330L and G331S mutations decrease binding to FcγRIIIa and FcγRIIb in the IgG1 Fc region.
These mutations play a crucial role in modulating antibody function for therapeutic applications.
A330L and G331S mutations decrease binding to FcγRIIIa and FcγRIIb in the IgG1 Fc region.
These mutations play a crucial role in modulating antibody function for therapeutic applications.
February 1, 2025 at 3:24 AM
7. AG Mutation:
A330L and G331S mutations decrease binding to FcγRIIIa and FcγRIIb in the IgG1 Fc region.
These mutations play a crucial role in modulating antibody function for therapeutic applications.
A330L and G331S mutations decrease binding to FcγRIIIa and FcγRIIb in the IgG1 Fc region.
These mutations play a crucial role in modulating antibody function for therapeutic applications.
5. TM Mutation:
T256E and T307E mutations affect glycosylation in the Fc region, reducing Fcγ receptor binding.
6. E333A Mutation:
E333A reduces Fcγ receptor binding, thereby suppressing antibody effector functions.
T256E and T307E mutations affect glycosylation in the Fc region, reducing Fcγ receptor binding.
6. E333A Mutation:
E333A reduces Fcγ receptor binding, thereby suppressing antibody effector functions.
February 1, 2025 at 3:24 AM
5. TM Mutation:
T256E and T307E mutations affect glycosylation in the Fc region, reducing Fcγ receptor binding.
6. E333A Mutation:
E333A reduces Fcγ receptor binding, thereby suppressing antibody effector functions.
T256E and T307E mutations affect glycosylation in the Fc region, reducing Fcγ receptor binding.
6. E333A Mutation:
E333A reduces Fcγ receptor binding, thereby suppressing antibody effector functions.
4. N297A Mutation:
The N297A mutation alters the glycosylation site in the Fc region, preventing glycan attachment. This reduces Fcγ receptor binding and ADCC activity. N297G has a similar effect.
The N297A mutation alters the glycosylation site in the Fc region, preventing glycan attachment. This reduces Fcγ receptor binding and ADCC activity. N297G has a similar effect.
February 1, 2025 at 3:24 AM
4. N297A Mutation:
The N297A mutation alters the glycosylation site in the Fc region, preventing glycan attachment. This reduces Fcγ receptor binding and ADCC activity. N297G has a similar effect.
The N297A mutation alters the glycosylation site in the Fc region, preventing glycan attachment. This reduces Fcγ receptor binding and ADCC activity. N297G has a similar effect.
3. LED Mutation:
A variant of LALA that includes L234A, L235A, and D265A, providing even stronger suppression of Fcγ receptor binding and effector functions.
A variant of LALA that includes L234A, L235A, and D265A, providing even stronger suppression of Fcγ receptor binding and effector functions.
February 1, 2025 at 3:24 AM
3. LED Mutation:
A variant of LALA that includes L234A, L235A, and D265A, providing even stronger suppression of Fcγ receptor binding and effector functions.
A variant of LALA that includes L234A, L235A, and D265A, providing even stronger suppression of Fcγ receptor binding and effector functions.
2. LALAPG Mutation:
A combination of L234A, L235A, D265A, P238S, and G239D mutations. These modifications further reduce Fcγ receptor and C1q binding, effectively suppressing effector functions.
A combination of L234A, L235A, D265A, P238S, and G239D mutations. These modifications further reduce Fcγ receptor and C1q binding, effectively suppressing effector functions.
February 1, 2025 at 3:24 AM
2. LALAPG Mutation:
A combination of L234A, L235A, D265A, P238S, and G239D mutations. These modifications further reduce Fcγ receptor and C1q binding, effectively suppressing effector functions.
A combination of L234A, L235A, D265A, P238S, and G239D mutations. These modifications further reduce Fcγ receptor and C1q binding, effectively suppressing effector functions.
1. LALA Mutation:
The most well-known mutation, involving L234A and L235A. It reduces binding to Fcγ receptors, thereby suppressing effector functions such as ADCC and CDC. This mutation has already been applied in multiple therapeutic antibodies.
The most well-known mutation, involving L234A and L235A. It reduces binding to Fcγ receptors, thereby suppressing effector functions such as ADCC and CDC. This mutation has already been applied in multiple therapeutic antibodies.
February 1, 2025 at 3:24 AM
1. LALA Mutation:
The most well-known mutation, involving L234A and L235A. It reduces binding to Fcγ receptors, thereby suppressing effector functions such as ADCC and CDC. This mutation has already been applied in multiple therapeutic antibodies.
The most well-known mutation, involving L234A and L235A. It reduces binding to Fcγ receptors, thereby suppressing effector functions such as ADCC and CDC. This mutation has already been applied in multiple therapeutic antibodies.
Several well-known mutations are used to silence the Fc region. Below is a summary of representative mutations.
February 1, 2025 at 3:24 AM
Several well-known mutations are used to silence the Fc region. Below is a summary of representative mutations.
Among the 756 antibodies containing an Fc domain:
- 339 consist of an IgG2 or IgG4 Fc domain or a mutated IgG1 Fc domain, leading to Fc silencing.
- Multispecific antibodies are more likely to be silenced, with 51 out of 67 being silenced when limited to those containing an Fc domain.
- 339 consist of an IgG2 or IgG4 Fc domain or a mutated IgG1 Fc domain, leading to Fc silencing.
- Multispecific antibodies are more likely to be silenced, with 51 out of 67 being silenced when limited to those containing an Fc domain.
February 1, 2025 at 3:24 AM
Among the 756 antibodies containing an Fc domain:
- 339 consist of an IgG2 or IgG4 Fc domain or a mutated IgG1 Fc domain, leading to Fc silencing.
- Multispecific antibodies are more likely to be silenced, with 51 out of 67 being silenced when limited to those containing an Fc domain.
- 339 consist of an IgG2 or IgG4 Fc domain or a mutated IgG1 Fc domain, leading to Fc silencing.
- Multispecific antibodies are more likely to be silenced, with 51 out of 67 being silenced when limited to those containing an Fc domain.
As a result, 57 antibody formats and 90 constant region variants were categorized. The discussion on Fc is particularly interesting, as follows:
Out of 804 antibodies, 48 completely lack the Fc domain, likely aiming for Fc silencing, reduced half-life, or improved tumor penetration.
Out of 804 antibodies, 48 completely lack the Fc domain, likely aiming for Fc silencing, reduced half-life, or improved tumor penetration.
February 1, 2025 at 3:24 AM
As a result, 57 antibody formats and 90 constant region variants were categorized. The discussion on Fc is particularly interesting, as follows:
Out of 804 antibodies, 48 completely lack the Fc domain, likely aiming for Fc silencing, reduced half-life, or improved tumor penetration.
Out of 804 antibodies, 48 completely lack the Fc domain, likely aiming for Fc silencing, reduced half-life, or improved tumor penetration.
Thank you for sharing this! I absolutely love your beautiful cartoon of the mushroom and amanitin-ADCs—such a creative and insightful depiction!
January 29, 2025 at 7:52 AM
Thank you for sharing this! I absolutely love your beautiful cartoon of the mushroom and amanitin-ADCs—such a creative and insightful depiction!
Interestingly, guanidine often fails where arginine succeeds, emphasizing the unique importance of arginine in these applications.
academic.oup.com/abt/article/...
academic.oup.com/abt/article/...
Effects of arginine in therapeutic protein formulations: a decade review and perspectives
Statement of Significance: Beneficial and detrimental effects of arginine in therapeutic protein formulations are reviewed and perspectives are provided.
academic.oup.com
January 26, 2025 at 7:55 AM
Interestingly, guanidine often fails where arginine succeeds, emphasizing the unique importance of arginine in these applications.
academic.oup.com/abt/article/...
academic.oup.com/abt/article/...
This is a review on click chemistry, published in *Bioconjugate Chemistry* (Open Access).
pubs.acs.org/doi/10.1021/...
pubs.acs.org/doi/10.1021/...
Click Chemistry: Reaction Rates and Their Suitability for Biomedical Applications
Click chemistry has become a commonly used synthetic method due to the simplicity, efficiency, and high selectivity of this class of chemical reactions. Since their initial discovery, further click chemistry methods have been identified and added to the toolbox of click chemistry reactions for biomedical applications. However, selecting the most suitable reaction for a specific application is often challenging, as multiple factors must be considered, including selectivity, reactivity, biocompatibility, and stability. Thus, this review provides an overview of the benefits and limitations of well-established click chemistry reactions with a particular focus on the importance of considering reaction rates, an often overlooked criterion with little available guidance. The importance of understanding each click chemistry reaction beyond simply the reaction speed is discussed comprehensively with reference to recent biomedical research which utilized click chemistry. This review aims to provide a practical resource for researchers to guide the selection of click chemistry classes for different biomedical applications.
pubs.acs.org
January 26, 2025 at 7:49 AM
This is a review on click chemistry, published in *Bioconjugate Chemistry* (Open Access).
pubs.acs.org/doi/10.1021/...
pubs.acs.org/doi/10.1021/...