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Biomedical subjects

J Choay

Publications and source records attributed to J Choay.

At least 91 records · Page 5Linked to original sources
PubMed1979

Enhancement of certain biological activities of muramyl dipeptide derivatives after conjugation to a multi-poly(DL-alanine)--poly(L-lysine) carrier.

N-Acetylmuramyl-L-Ala-D-Glu-NH2 (muramyl dipeptide) and several of its derivatives are effective immunoactivators that can enhance nonspecific resistance to infection but can also elicit fever. In contrast, one of its stereoisomers, N-acetylmuramyl-D-Ala-D-Glu-NH2, is devoid of both these activities. Our present report demonstrates that macromolecularization of muramyl dipeptide by attachment of several units to a multi-poly(DL-Ala)-poly(L-Lys) carrier potentiates both its pyrogenic and its immunostimulant activity. This branched polymer has been extensively used as carrier to various haptens. Surprisingly, inactive N-acetylmuramyl-D-Ala-D-Glu-NH2, after conjugation under the same conditions, becomes capable of increasing nonspecific immunity although its lack of pyrogenicity is not greatly modified. Moreover, the N-acetylmuramyl-D-Ala-D-Glu--NH2 conjugate remains devoid of adjuvant, sensitizing, or eliciting activity.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1979

Synthesis of N-acetyl-muramyl-L-alanyl-D-glutamic-alpha-amide(MDP) or -alpha-methyl ester derivatives, bearing a lipophilic group at the C-terminal peptide end.

We report the synthesis of nine lipophilic derivatives of N-acetyl-muramyl-L-alanyl-D-glutamic-alpha-amide (MDP) or -alpha-methyl ester in which the gamma-carboxyl function of the D-glutamyl residue is either esterified by a medium chain alcohol or substituted by an L-alanyl residue esterified by a medium or long chain alcohol. A new method is described which easily allows one to obtain derivatives of MDP, bearing a free or substituted amino-acyl or peptidyl residue on the gamma-carboxyl function.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1978

In vivo and in vitro stimulation of nonspecific immunity by the beta-D-p-aminophenyl glycoside of N-acetylmuramyl-L-alanyl-D-isoglutamine and an oligomer prepared by cross-linking with glutaraldehyde.

Several biological activities of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP for muramyl dipeptide), a synthetic immunoadjuvant, are inhibited after glycosidation with p-aminophenol. Thus, this glycoside does not induce an increase humoral antibody response in mice when injected in saline, although it retains its stimulatory effect on circulating antibodies and delayed hypersensitivity after administration in a water-in-oil emulsion. The capacity of MDP to stimulate mouse spleen cells is lost, and, moreover, the analogue is unable to increase nonspecific resistance to infection under conditions where MDP is active. After cross-linking of the beta-D-p-aminophenyl glycoside of MDP with glutaraldehyde, several biological activities of MDP are recovered. Moreover, the cross-linked oligomer (molecular weight, approximately 6,000 daltons) is able to stimulate the uptake of thymidine by spleen cells from a strain of mice weakly responsive to MDP and is more active than MDP in protecting mice against bacterial challenge.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1977

Enhancement of nonspecific immunity to Klebsiella pneumoniae infection by a synthetic immunoadjuvant (N-acetylmuramyl-L-alanyl-D-isoglutamine) and several analogs.

N-Acetylmuramyl-L-alanyl-D-isoglutamine and four other synthetic adjuvants that are structural analogs of part of the mycobacterial peptidoglycan monomer are shown to enhance the nonspecific immunity of mice infected by Klebsiella pneumoniae. These compounds are active by various routes, including oral administration; they are also effective when administered after challenge. Of the seventeen other analogs tested, none is able to increase significantly resistance to infection, although seven of these molecules are adjuvant-active in saline. Previous results have shown that in contrast to lipopolysaccharides, these synthetic adjuvants are devoid of immunogenicity, mitogenicity, and toxicity in normal or adrenalectomized mice.

Adjuvants, Immunologic↗
PubMed1976

Modulation of the immune response by a synthetic adjuvant and analogs.

N-Acetylmuramyl-L-alanyl-D-isoglutamine increases the humoral immune response of mice when given in aqueous media instead of the usual water-in-oil emulsions. Moreover, this compound is adjuvant active even by the oral route. In view of studying the relation between chemical structure and biological activity, several synthetic analogs were tested. The immune response could be modulated according to chemical modifications, and the synthetic analog with D- in place of L-alanine was shown to inhibit the immune response.

Adjuvants, Immunologic↗