Tags

Type your tag names separated by a space and hit enter

Methyl acetyl phosphate, a new type of antisickling agent: site-specific acetylating agent toward the 2,3-DPG binding site in hemoglobin S.
Am J Pediatr Hematol Oncol. 1988 Winter; 10(4):348-50.AJ

Abstract

Methyl acetyl phosphate inhibits the sickling of erythrocytes in vitro. Its mechanism of action is through the selective acetylation of some of the amino groups at the 2,3-diphosphoglycerate (2,3-DPG) binding site of the hemoglobin molecule. Only 3 of a total 24 amino groups per alpha beta-dimer of hemoglobin are reactive. These groups are Val-1, Lys-82, and Lys-144 on the beta-chain of hemoglobin. None of the groups on the alpha-chain are acetylated. Acetylated hemoglobin S has an increased solubility as well as a reduced ability to bind to 2,3-DPG. Methyl acetyl phosphate is able to penetrate the erythrocyte membrane and successfully acetylate intracellular hemoglobin S without causing cell lysis. Sickle erythrocytes treated with methyl acetyl phosphate maintain an oxy-like profile of cell density distribution in a phthalate ester gradient. The oxygen binding property of erythrocytes after the treatment with methyl acetyl phosphate is not changed significantly from that of untreated cells. Our in vitro results indicate that further preclinical testing of methyl acetyl phosphate in sickle cell anemia is warranted.

Authors+Show Affiliations

Rockefeller University, New York, NY 10021.No affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

3239714

Citation

Ueno, H, and J M. Manning. "Methyl Acetyl Phosphate, a New Type of Antisickling Agent: Site-specific Acetylating Agent Toward the 2,3-DPG Binding Site in Hemoglobin S." The American Journal of Pediatric Hematology/oncology, vol. 10, no. 4, 1988, pp. 348-50.
Ueno H, Manning JM. Methyl acetyl phosphate, a new type of antisickling agent: site-specific acetylating agent toward the 2,3-DPG binding site in hemoglobin S. Am J Pediatr Hematol Oncol. 1988;10(4):348-50.
Ueno, H., & Manning, J. M. (1988). Methyl acetyl phosphate, a new type of antisickling agent: site-specific acetylating agent toward the 2,3-DPG binding site in hemoglobin S. The American Journal of Pediatric Hematology/oncology, 10(4), 348-50.
Ueno H, Manning JM. Methyl Acetyl Phosphate, a New Type of Antisickling Agent: Site-specific Acetylating Agent Toward the 2,3-DPG Binding Site in Hemoglobin S. Am J Pediatr Hematol Oncol. 1988;10(4):348-50. PubMed PMID: 3239714.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Methyl acetyl phosphate, a new type of antisickling agent: site-specific acetylating agent toward the 2,3-DPG binding site in hemoglobin S. AU - Ueno,H, AU - Manning,J M, PY - 1988/1/1/pubmed PY - 1988/1/1/medline PY - 1988/1/1/entrez SP - 348 EP - 50 JF - The American journal of pediatric hematology/oncology JO - Am J Pediatr Hematol Oncol VL - 10 IS - 4 N2 - Methyl acetyl phosphate inhibits the sickling of erythrocytes in vitro. Its mechanism of action is through the selective acetylation of some of the amino groups at the 2,3-diphosphoglycerate (2,3-DPG) binding site of the hemoglobin molecule. Only 3 of a total 24 amino groups per alpha beta-dimer of hemoglobin are reactive. These groups are Val-1, Lys-82, and Lys-144 on the beta-chain of hemoglobin. None of the groups on the alpha-chain are acetylated. Acetylated hemoglobin S has an increased solubility as well as a reduced ability to bind to 2,3-DPG. Methyl acetyl phosphate is able to penetrate the erythrocyte membrane and successfully acetylate intracellular hemoglobin S without causing cell lysis. Sickle erythrocytes treated with methyl acetyl phosphate maintain an oxy-like profile of cell density distribution in a phthalate ester gradient. The oxygen binding property of erythrocytes after the treatment with methyl acetyl phosphate is not changed significantly from that of untreated cells. Our in vitro results indicate that further preclinical testing of methyl acetyl phosphate in sickle cell anemia is warranted. SN - 0192-8562 UR - https://www.unboundmedicine.com/medline/citation/3239714/Methyl_acetyl_phosphate_a_new_type_of_antisickling_agent:_site_specific_acetylating_agent_toward_the_23_DPG_binding_site_in_hemoglobin_S_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=3239714.ui DB - PRIME DP - Unbound Medicine ER -