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Biomedical subjects

M Morpurgo

Publications and source records attributed to M Morpurgo.

98 records · Page 6Linked to original sources
PubMedDate not supplied

A branched monomethoxypoly(ethylene glycol) for protein modification.

Procedures are described for linking monomethoxypoly(ethylene glycol) (mPEG) to both epsilon and alpha amino groups of lysine. The lysine carboxyl group can then be activated as a succinimidyl ester to obtain a new mPEG derivative (mPEG2-COOSu) with improved properties for biotechnical applications. This branched reagent showed in some cases a lower reactivity toward protein amino groups than the linear mPEG from which it was derived. A comparison of mPEG- and mPEG2-modified enzymes (ribonuclease, catalase, asparaginase, trypsin) was carried out for activity, pH and temperature stability, Km and Kcat values, and protection to proteolytic digestion. Most of the adducts from mPEG and mPEG2 modification presented similar activity and stability toward temperature change and pH change, although in a few cases mPEG2 modification was found to increase temperature stability and to widen the range of pH stability of the adducts. On the other hand, all of the enzymes modified with the branched polymer presented greater stability to proteolytic digestion relative to those modified with the linear mPEG. A further advantage of this branched mPEG lies in the possibility of a precise evaluation of the number of polymer molecules bound to the proteins; upon acid hydrolysis, each molecule of mPEG2 releases a molecule of lysine which can be detected by amino acid analysis. Finally, dimerization of mPEG by coupling to lysine provides a needed route to monofunctional PEGs of high molecular weight.

Asparaginase↗
PubMedDate not supplied

Preparation of characterization of poly(ethylene glycol) vinyl sulfone.

Synthesis of the vinyl sulfone and chloroethyl sulfone derivatives of poly(ethylene glycol) (PEG) is described. The chloroethyl sulfone (CES-PEG) is rapidly converted to the vinyl sulfone (VS-PEG) in the presence of base but is stable in water at neutral pH. Reactions with small molecules such as beta-mercaptoethanol and N alpha-acetyllysine show that the vinyl sulfone derivative is highly selective for reaction with sulfhydryl groups relative to reaction with amino groups. Also, VS-PEG is stable in water. These properties indicate that VS-PEG should be useful for selective attachment of PEG to protein cysteine groups. This hypothesis was verified by reacting VS-PEG with cysteine groups of reduced ribonuclease (RNase); the reaction is rapid and selective at pH 7-9. Reaction at lysine sites of unreduced RNase occurs slowly at pH 9.3 and is essentially complete after 100 h. Amino acid residues other than lysine and cysteine are not reactive toward VS-PEG. The covalent linkage between VS-PEG and lysine or cysteine groups is shown to be stable.

Amines↗
PubMedDate not supplied

Echocardiographic aspects of pulmonary arterial hypertension in chronic lung disease.

An echocardiographic M-mode study has been performed on 58 patients with pulmonary arterial hypertension at rest or on exercise, with chronic lung disease, either obstructive (41 cases of COLD) or restrictive (17 cases of interstitial lung disease, ILD) in nature. The average Ppa was practically the same (i.e. 27.3 +/- 11.7 mmHg and 26.0 +/- 8.0 mmHg respectively) in the two groups of patients, even though the COLD patients were older than the ILD patients (58.7 +/- 9.3 vs 38 +/- 11 years). The echo detection of the pulmonary valve was successful in only 35% of COLD patients and in 86% of ILD patients (p less than 0.01). A multiple regression analysis disclosed a rather weak, but nevertheless statistically significant, correlation (p less than 0.01) between 1) Ppa and the ratio of right ventricular to left ventricular end-diastolic volume, and 2) between right ventricular end-diastolic pressure and septal systolic displacement. The standard error of estimated versus actual Ppa taking into account the ventricular and septal echo variables was as high as +/- 7.63 mmHg, thus preventing a reliable prediction of Ppa in individual cases. An echocardiographic pattern of pansystolic mitral valve prolapse was observed in 29% of ILD patients, but never in cases with COLD.

Cardiac Output↗