Abstract

The aim of this work is to provide a better understanding of the mechanism of the polymerization and depolymerization of sickle Hb. The kinetics and thermodynamcis of the polymerization of various Hbs will be studied. To elucidate the nature of nuceli, changes in molecular propperties of Hb S and mixtures of sickle and non-sickle Hbs during the pregelation period will be measured by a low angle laser light scattering photometer under various experimental conditions. The applicants will also prepare oligomers of Hb S which are cross-linked during the nucleation step and investigatae whether these cross-linked oligomers can act as nuclei. The role of hybrid Hbs formed from sickle and non-sickle Hbs will be studied. The applicant and co-workers recently succeeded in chemically connecting two unlike chains intramolecularly with corss-linking agents, one of which is bis (3,5 dibromosalicyl) fumarate. I will the nature of the interaction of Hb S, Hb X during polymerization. Our studies on the polymerization of sickle and non-sickle Hbs suggested that there are many types of interactions between non-sickle nonomeric Hb and nuclei formed from Hb S. The nature of these interactions will be studied.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL032908-02
Application #
3344460
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1984-06-01
Project End
1987-05-31
Budget Start
1985-06-01
Budget End
1986-05-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Reddy, L R; Reddy, K S; Surrey, S et al. (1997) Role of beta87 Thr in the beta6 Val acceptor site during deoxy Hb S polymerization. Biochemistry 36:15992-8
Adachi, K; Konitzer, P; Paulraj, C G et al. (1994) Role of Leu-beta 88 in the hydrophobic acceptor pocket for Val-beta 6 during hemoglobin S polymerization. J Biol Chem 269:17477-80
Adachi, K; Reddy, L R; Surrey, S (1994) Role of hydrophobicity of phenylalanine beta 85 and leucine beta 88 in the acceptor pocket for valine beta 6 during hemoglobin S polymerization. J Biol Chem 269:31563-6
Adachi, K; Konitzer, P; Surrey, S (1994) Role of gamma 87 Gln in the inhibition of hemoglobin S polymerization by hemoglobin F. J Biol Chem 269:9562-7
Yamashiro, D J; Adachi, M; Konitzer, P et al. (1994) Polymerization and instability of a recombinant hemoglobin containing valine beta 7. J Biol Chem 269:23996-9
Adachi, K; Lai, C H; Konitzer, P et al. (1994) Crystallization of recombinant hemoglobins with basic amino acid substitutions (Lys and Arg) at the beta 6 position. Blood 84:1309-13
Adachi, K; Surrey, S; Tamary, H et al. (1993) Hb Shelby [beta 131(H9)Gln-->Lys] in association with Hb S [beta 6(A3)Glu-->Val]: characterization, stability, and effects on Hb S polymerization. Hemoglobin 17:329-43
Adachi, K; Kim, J Y; Konitzer, P et al. (1993) Effects of beta 6 amino acid hydrophobicity on stability and solubility of hemoglobin tetramers. FEBS Lett 315:47-50
Adachi, K; Konitzer, P; Kim, J et al. (1993) Effects of beta 6 aromatic amino acids on polymerization and solubility of recombinant hemoglobins made in yeast. J Biol Chem 268:21650-6
Adachi, K; Konitzer, P; Lai, C H et al. (1992) Oxygen binding and other physical properties of human hemoglobin made in yeast. Protein Eng 5:807-10

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