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Biomedical subjects

M Fridkin

Publications and source records attributed to M Fridkin.

At least 199 records · Page 11Linked to original sources
PubMed1978

Tuftsin (an Ig-associated tetrapeptide) triggers the immunogenic function of macrophages: implications for activation of programmed cells.

The immunoglobulin heavy-chain-associated tetrapeptide, tuftsin (Thr-Lys-Pro-Arg), known for its phagocytosis-stimulating activity, was found to augment the antigen-specific, macrophage-dependent education of T lymphocytes. The investigation of stereospecific characteristics of the tetrapeptide, by use of structural analogs with different modifications, revealed strict structural requirements for eliciting the immunogenic activity of macrophages. It was found that the most important moiety for its activity is the dipeptide Pro-Arg. This finding is of interest in view of the appearance of this particular dipeptide in other bioregulatory peptides, including many of the peptide hormones. The significance of the appearance of a common structure in such molecules, which may act through specific receptors on different target cells, is discussed.

Amino Acid Sequence↗
PubMed1978

Thiolysis of Nim-2,4-dinitrophenyl-histidine peptides with 2-mercaptoethanol. An explannation for the pH optimum.

The thiolysis of Nim-2,4-dinitrophenyl-histidine peptides with 2-mercaptoethanol demonstrates an optimal rate between pH 8.5 and 9.0. Base lability of both reactants and product was investigated as a possible cause for the pH optimum. N-2,4-Dinitrophenylimidazole, a model for Nim-2,4-dinitrophenylhistidine peptides, 2-mercaptoethanol and the product of thiolysis, 2,4-dinitrophenyl-S-mercaptoethan-2-ol, were subjected to aqueous basic conditions (pH 8.5 to 12.0). The reactions were followed spectrophotometrically, and products were identified by comparison of their ultra-violet spectra with commercially available or synthetic compounds. Mechanisms and rate constants for base hydrolysis of 2,4-dinitrophenyl-thio ethers are presented. Although N-2,4-dinitrophenylimidazole and 2,4-dinitrophenyl-S-mercaptoethan-2-oldohydrolyze, it is the oxidation of 2-mercaptoethanol to 2-mercaptoethanol disulfide which results in the decreasing rate of thiolysis above pH 9.0.

Dinitrobenzenes↗
PubMed1978

Synthesis and biological activity of tuftsin and of [O = C Thr1]-tuftsin. A novel synthetic route to peptides containing N-terminal L -O = C Thr and L - O = C Ser residues.

The cyclization, under alkaline conditions, of N-benzyloxycarbonyl-L-threonine and of N-benzyloxycarbonyl-L-serine to produce 5-methyl-2-oxo-oxazolidine-4-carboxylic acid (O = C Thr1 and 2-oxo-oxazolidine-4-carboxylic acid (O = C Ser), respectively, was investigated and found to be efficient and racemization-free. Similar was the cyclization which accompanied the basic hydrolysis of N-benzyl-oxycarbonyl-L-threonyl-L-phenylalanine methyl ester and of N-benzyloxy-carbonyl-L-seryl-DL-valine ethyl ester, and which resulted in the formation of L - O = C Thr-L-Phe and L - O = C Ser-DL-Val, respectively. The reaction was applied to the synthesis of [O = C Thr1] tuftsin, an active analog of the phagocytosis stimulating peptide tuftsin. A new synthetic route to tuftsin is also described.

Amino Acid Sequence↗
PubMed1977

Decreased tuftsin concentrations in patients who have undergone splenectomy.

Serum tuftsin concentrations were measured, using a radioimmunoassay developed in Israel, in normal subjects and in patients who had undergone splenectomy. Concentrations in those who had undergone traumatic and elective splenectomy were much lower. The tuftsin concentration in 38 patients with Hodgkin's disease who had undergone splenectomy during staging laparotomy was not significantly different from the mean concentration in other patients who had had elective splenectomy. In four patients who underwent splenectomy for non-malignant haematological disorders measurements made before and after operation showed that tuftsin concentrations fell significantly in the days after operation. The increased susceptibility to overwhelming infections of patients with Hodgkin's disease and others who have undergone splenectomy may be related to the low tuftsin concentrations. As pre-splenectomy tuftsin concentrations in patients with Hodgkin's disease were normal, the practice of performing staging laparotomy and splenectomy in patients with Hodgkin's disease should perhaps be reconsidered.

Adult↗
PubMed1977

Gonadotropin-releasing hormone in milk.

The hypothalamic hormone gonadotropin-releasing hormone (GnRH) has been found in milk of man, cow, and rat. Radioimmunoassays of acidified milk indicate concentrations of GnRH ranging between 0.1 and 3 nanograms per milliliter. Multistep extractions, followed by electrophoresis, reveal gonadotropin-releasing activity in the fraction that comigrates with the GnRH-marker. A second hypothalamic hormone, thyrotropin-releasing hormone, is present in milk at a much lower concentration. "Milk -GnRH" may influence the secretion of the gonadotropic hormones in neonates.

Animals↗
PubMed1977

On the role of tryptophan in luteinizing-hormone-releasing hormone (luliberin).

The tryptophan residue of luteinizing-hormone-releasing hormone (luliberin) was chemically modified to produce the following analogs: [Trp(o)3]luliberin, Trp-(2,4-dinitrophenylsulfenyl)-luliberin, Trp-(2-hydroxy-5-nitrobenzyl)luliberin, (Trp-S-luliberin)2, Trp-CH3S-luliberin and Trp-formyl-luliberin. The luteinizing-hormone-releasing activity of those analogs was determined by bioassay in vitro and found to be 0.2%, 0.2%, 0.6%, 1.5%, 1.7% and 7% of that of the natural hormone, respectively. These results demonstrate that alterations in the indole moiety of tryptophan-3, which lead to a reduction in its electron density or sterically restrict its electron avaliability, are associated with a dramatic loss of biological activity.

Animals↗
PubMed1977

Tuftsin and some analogs: synthesis and interaction with human polymorphonuclear leukocytes.

The phagocytosis-stimulating tetrapeptide tuftsin, L-threonyl-L-lysyl-L-prolyl-L-arginine, was synthesized by both conventional and polymeric-reagent approaches. Using a combination of the two methods several analogs were prepared, including: [Ala1]tuftsin, [Lys1]tuftsin, [Ser1]tuftsin, [Val1]tuftsin, acetyl-tuftsin, p-aminophenylacetyl-tuftsin and tyrosyl-tuftsin. [Des-Thr1]tuftsin and [omega-NO2(4)]tuftsin were synthesized using a conventional procedure. The effects of synthetic peptides on the phagocytosis of heat-killed yeasts and on the reduction of the dye nitroblue tetrazolium by normal human polymorphonuclear leukocytes were investigated. Tuftsin and to a lesser extent [Lys1]tuftsin and [Ser1]tuftsin were found to stimulate phagocytosis, whereas the other analogs synthesized as well as [Ser1]tuftsin exhibited inhibitory effects to tuftsin's action. Tuftsin alone has stimulated nitroblue tetrazolium reduction; [Des-Thr1]tuftsin and [Ala1]tuftsin repressed this stimulation, while the other peptides showed no effect.

Hexosephosphates↗
PubMed1977

A photolabile protecting group for the phenolic hydroxyl function of tyrosine.

The ortho-nitrobenzyl group (ONBzl) was utilized to protect the phenolic functions of the side chain of tyrosine. Optimal conditions for its mild photolyti removal were established. This paper describes the preparation and properties of some (O-ONBzl)-tyrosine derivatives of potential value in the synthesis of tyrosine-containing peptides. Their use in the synthesis of the dipeptide, N-benzyloxycarbonyl-L-tyrosyl-glycine ethyl ester is presented as an example.

Benzyl Compounds↗
PubMed1977

Purification of the gonadotropin-releasing hormone-degrading enzyme by affinity chromatography.

A crude preparation of Kallikrein inactivator, which inhibits the gonadotropin-releasing hormone (GnRH)-degrading enzyme(s) from rat hypothalamus and anterior pituitary, was fractionated by passage through an ion-exchange column. The enzyme-inhibiting fraction was coupled to Sepharose and the resin obtained was used for, affinity-chromatography purification of the GnRH-degrading enzyme. The enzyme from crude tissue preparations was retained on this column and eluted by 0.05 M phosphate buffer. A 9-12 fold increase in the specific activity of the enzyme was achieved. Bacitracin, an effective peptide inhibitor of the degradation of GnRH, was also coupled to Sepharose. Three different such Sepharose-bacitracin conjugates were synthesized, two of which inhibited the degradation of GnRH by hypothalamic and pituitary extracts. They all failed, however, to separate the active enzymic fraction from the bulk of accompanying proteins, using affinity chromatographic techniques.

Animals↗
PubMed1976

Structure-activity relationships of luliberin substituted at position 8.

Substitution of arginine at position 8 of luliberin by the basic amino acids homoarginine, lysine and diaminobutyric acid resulted in analogues in which the luteinizing hormone-releasing activity is markedly reduced, whereas the cross reactivity with specific antibodies to luliberin is preserved. Fluorimetric titrations of these analogues, carried out as with luliberin, revealed pK values of 6.00 +/- 0.05 and of 9.75 +/- 0.15 for His 2 and Try 5 respectively which are essentially the same as in luliberin. However, the rate of collisions between the side chains of His 2 and Trp 3 in these analogues was found to decrease by 36-39%. Substitution at position 8 with the non-basic amino acid omega-nitro arginine yielded an analogue possessing a very low hormonal activity as well as poor recognition of antibodies specific to luliberin. The fluorescence properties of this peptide are markedly different from those of luliberin and its three basic analogues. These results indicate that the functional integrity of the active unit His 2 . . . Tyr 5 . . . Arg 8 in luliberin depends both on size and basicity of the amino acid side chain at position 8.

Amino Acids, Diamino↗
PubMed1976

Structural features of luliberin (luteinising hormone-releasing factor) inferred from fluorescence measurements.

The fluorescence and excitation spectra of luliberin (luteinizing hormone-releasing factor) in 0.005 M aqueous ammonium acetate are identical in shape to those of N-acetyltryptophan amide and are related to the indole side chain of Trp3. The change of fluoresecence intensity of luliberin with pH was measured in the range of pH 4-11. The increase of pH from 4 to 7.5 is followed by about 50% increase in fluorescence intensity due to deprotonation of the imidazolium side chain of His2. The fluorimetric titration curve in this pH region reveals a pK value for His2 of 5.95. Increasing of pH from 8 to 11 results in about 40% quenching of the fluorescence due to electronic energy transfer from the excited indole of Trp3 to the phenolate side chain of Tyr5. The pK value of Tyr5, obtained independently from the fluorimetric and photometric titrations indicate that at pH 7-8 luliberin contains only one charged residue, Arg8, which is in close vicinity to both His2 and Tyr5. The side chains of His2, Tyr5 and Arg8 presumably form a combined unit which may play an active role in the hormone action. Trp3 is at a maximal distance from this unit and may thus act as an independent active unit.

Gonadotropin-Releasing Hormone↗