Hemoglobin Variants as Targets for Stabilizing Drugs

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F10974938%3A_____%2F25%3A25_88_36" target="_blank" >RIV/10974938:_____/25:25_88_36 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.3390/molecules30020385" target="_blank" >https://doi.org/10.3390/molecules30020385</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/molecules30020385" target="_blank" >10.3390/molecules30020385</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Hemoglobin Variants as Targets for Stabilizing Drugs

Popis výsledku v původním jazyce

Hemoglobin is an oxygen-transport protein in red blood cells that interacts with multiple ligands, e.g., oxygen, carbon dioxide, carbon monoxide, and nitric oxide. Genetic variations in hemoglobin chains, such as those underlying sickle cell disease and thalassemias, present substantial clinical challenges. Here, we review the progress in research, including the use of allosteric modulators, pharmacological chaperones, and antioxidant treatments, which has begun to improve hemoglobin stability and oxygen affinity. According to UniProt (as of 7 August 2024), 819 variants of the alpha-hemoglobin subunit and 771 variants of the beta-hemoglobin subunit have been documented, with over 116 classified as unstable. These data demonstrate the urgent need to develop variant-specific stabilizing options. Beyond small-molecule drugs/binders, novel protein-based strategies-such as engineered hemoglobin-binding proteins (including falcilysin, llama-derived nanobodies, and alpha-hemoglobin-stabilizing proteins)-offer promising new options. As our understanding of hemoglobin's structural and functional diversity grows, so does the potential for genotype-driven approaches. Continued research into hemoglobin stabilization and ligand-binding modification may yield more precise, effective treatments and pave the way toward effective strategies for hemoglobinopathies.

Název v anglickém jazyce

Hemoglobin Variants as Targets for Stabilizing Drugs

Popis výsledku anglicky

Hemoglobin is an oxygen-transport protein in red blood cells that interacts with multiple ligands, e.g., oxygen, carbon dioxide, carbon monoxide, and nitric oxide. Genetic variations in hemoglobin chains, such as those underlying sickle cell disease and thalassemias, present substantial clinical challenges. Here, we review the progress in research, including the use of allosteric modulators, pharmacological chaperones, and antioxidant treatments, which has begun to improve hemoglobin stability and oxygen affinity. According to UniProt (as of 7 August 2024), 819 variants of the alpha-hemoglobin subunit and 771 variants of the beta-hemoglobin subunit have been documented, with over 116 classified as unstable. These data demonstrate the urgent need to develop variant-specific stabilizing options. Beyond small-molecule drugs/binders, novel protein-based strategies-such as engineered hemoglobin-binding proteins (including falcilysin, llama-derived nanobodies, and alpha-hemoglobin-stabilizing proteins)-offer promising new options. As our understanding of hemoglobin's structural and functional diversity grows, so does the potential for genotype-driven approaches. Continued research into hemoglobin stabilization and ligand-binding modification may yield more precise, effective treatments and pave the way toward effective strategies for hemoglobinopathies.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10610 - Biophysics

Projekt

—

Návaznosti

R - Projekt Ramcoveho programu EK

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Molecules

ISSN

—

e-ISSN

1420-3049

Svazek periodika

30

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

34

Strana od-do

385 (1-34)

Kód UT WoS článku

001404360600001

EID výsledku v databázi Scopus

2-s2.0-85216224909