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Biomedical subjects

S Lovas

Publications and source records attributed to S Lovas.

33 records · Page 2Linked to original sources
PubMed1997

Synthesis of gonadotropin-releasing hormone III analogs. Structure-antitumor activity relationships.

Following the observation that the activity of gonadotropin-releasing hormone III (GnRH-III) in the suppression of growth of MDA-MB-231 and MCF-7 breast cancer cells surpasses that of GnRH and other analogs thereof, analogs of GnRH-III were synthesized to investigate the structural basis for the improved antitumor activity. Compounds synthesized include analogs with changes in the central sequence in which GnRH-III differs from GnRH and in the C- and N-terminal regions. The results indicate that a salt bridge between Asp6 and Lys8 stabilizes the active conformation of GnRH-III and show the importance of the Trp7. Replacement of the C-terminal Gly-NH2 with D-Ala-NH2 was not well tolerated, but replacement with ethylamide was. Replacement of pGlu1 with Ac-D-Trp appears to have a significantly deleterious effect on a unique conformation of GnRH-III which is responsible for its binding to the receptors on cancer cell lines and the resultant antitumor activity.

Antineoplastic Agents↗
PubMed1995

Radioimmunoassay of the APC gene product using antibodies against its middle and carboxyl regions.

A radioimmunoassay (RIA) has been developed for the adenomatous polyposis coli protein (APC). High-avidity rabbit polyclonal antibodies were produced against synthetic peptides corresponding to amino acids 1865-1881 (APC-1) and to amino acids 1336-1350 (APC-2) in APC's 2844 amino acid sequence. Both antibodies were utilized in RIA to evaluate full-length APC that is present in the insoluble particulate fraction of cell lysates. High salt extraction, often employed for coiled-coil type protein preparations, was found to be useful for extraction of APC from lysates of normal colonic epithelium. Proteolytic digestion of high salt extracts increased antibody reactivity toward both epitopes, suggesting that APC-1 and APC-2 antigenic sites are partially concealed due to APC's involvement in multiprotein complexes. Thus, RIA using our antibodies will provide a valuable tool for APC protein purification and in studies for elucidating APC's biologic function.

Adenomatous Polyposis Coli Protein↗
PubMed1994

Aspartate-bond isomerization affects the major conformations of synthetic peptides.

The aspartic acid bond changes to an beta-aspartate bond frequently as a side-reaction during peptide synthesis and often as a post-translational modification of proteins. The formation of beta-asparate bonds is reported to play a major role not only in protein metabolism, activation and deactivation, but also in pathological processes such as deposition of the neuritic plaques of Alzheimer's disease. Recently, we reported how conformational changes following the aspartic-acid-bond isomerization may help the selective aggregation and retention of the amyloid beta peptide in affected brains (Fabian et al., 1994). In the current study we used circular dichroism, Fourier-transform infrared spectroscopy, and molecular modeling to characterize the general effect of the beta-aspartate-bond formation on the conformation of five sets of synthetic model peptides. Each of the non-modified, parent peptides has one of the major secondary structures as the dominant spectroscopically determined conformation: a type I beta turn, a type II beta turn, short segments of alpha or 3(10) helices, or extended beta strands. We found that both types of turn structures are stabilized by the aspartic acid-bond isomerization. The isomerization at a terminal position did not affect the helix propensity, but placing it in mid-chain broke both the helix and the beta-pleated sheet with the formation of reverse turns. The alteration of the geometry of the lowest energy reverse turn was also supported by molecular dynamics calculations. The tendency of the aspartic acid-bond isomerization to stabilize turns is very similar to the effect of incorporating sugars into synthetic peptides and suggests a common feature of these post-translational modifications in defining the secondary structure of protein fragments.

Amino Acid Sequence↗
PubMed1993

Neuropeptide gamma-(1-9)-peptide: a major product of the posttranslational processing of gamma-preprotachykinin in rat tissues.

gamma-Preprotachykinin mRNA is the most abundant tachykinin mRNA in rat tissues, but the pathway of post-translational processing of its translation product is unknown. An antiserum was raised against the synthetic peptide Asp-Ala-Gly-His-Gly-Gln-Ile-Ser-His [neuropeptide gamma-(1-9)-peptide, equivalent to gamma-preprotachykinin-(72-80)-peptide], that showed < 1% reactivity with intact neuropeptide gamma and other tachykinins. Neuropeptide gamma-(1-9)-peptide was detected by radioimmunoassay in relatively high concentrations in extracts of regions of rat brain and gastrointestinal tract. These concentrations correlated with (r = 0.99), but were significantly (p < 0.05) less than, the concentrations of neurokinin A-like immunoreactivity. The neuropeptide gamma-(1-9)-like immunoreactivity in an extract of rat brain was eluted from a reverse-phase HPLC column in a single fraction with the same retention time as synthetic neuropeptide gamma-(1-9)-peptide. The synthetic peptide did not contract or relax isolated rat trachea, superior mesenteric artery, stomach fundus, or ileum, and the peptide did not affect the ability of neuropeptide gamma to contract the rat fundus. It is concluded that, in rat tissues, Lys70-Arg71 in gamma-preprotachykinin is a major site of posttranslational processing, but the resulting product, neuropeptide gamma-(1-9)-peptide, is neither an agonist nor an antagonist at the neurokinin-2 (NK-2) receptor.

Animals↗
PubMed1993

Primary structure and biological activity of a third gonadotropin-releasing hormone from lamprey brain.

Previous studies have led to the identification of two molecular forms of GnRH (GnRH-I and II) in the brain of the sea lamprey, Petromyzon marinus. From analysis of these two forms, the primary structure of GnRH-I and the amino acid composition of GnRH-II were determined. We have now isolated a third molecular form of GnRH (GnRH-III) from the brain of this species that is different from GnRH-I and -II. The primary structure of GnRH-III is pGlu-His-Trp-Ser-His-Asp-Trp-Lys- Pro-Gly-NH2. A synthetic decapeptide with this amino acid sequence was chromatographically identical to natural GnRH-III. Intraperitoneal injection of synthetic lamprey GnRH-III (0.1 microgram/g) produced a significant (P < 0.05) elevation of plasma progesterone (31% over basal values) in female lampreys that was comparable to that produced by the same dose of lamprey GnRH-I (36% over basal). The elevation in plasma estradiol produced by lamprey GnRH-III (244% over basal) was significantly (P < 0.05) less than the elevation produced by GnRH-I (322% over basal). We propose based on the biological activity of lamprey GnRH-III in these studies and the occurrence of this peptide during metamorphosis in lampreys, that both lamprey GnRH-I and -III are neurohormones involved in reproduction in lampreys.

Amino Acid Sequence↗
PubMed1992

Primary structure and receptor-binding properties of a neurokinin A-related peptide from frog gut.

A tachykinin peptide was isolated from an extract of the intestine of the European green frog, Rana ridibunda, and its primary structure was established as: His-Lys-Leu-Asp-Ser-Phe-Ile-Gly-Leu-Met.CONH2. This sequence was confirmed by chemical synthesis and shows two amino acid substitutions (leucine for threonine at position 3 and isoleucine for valine at position 7) compared with neurokinin A. Binding parameters for synthetic [Leu3,Ile7]neurokinin A and mammalian tachykinins were compared using receptor-selective radioligands and crude membranes from tissues enriched in the NK1, NK2 and NK3 receptors. [Leu3,Ile7]Neurokinin A was approx. 3-fold less potent than substance P in inhibiting the binding of 125I-labelled [Sar9,Met(O2)11]substance P (labelled with Bolton-Hunter reagent) to rat submandibular gland (NK1 receptor), 8-fold less potent than neurokinin A in inhibiting the binding of [2-[125I]iodohistidine1]neurokinin A to rat stomach fundus (NK2 receptor) and 6-fold less potent than neurokinin B in inhibiting the binding of 125I-Bolton-Hunter-labelled scyliorhinin II to rat brain (NK3 receptor). Thus the frog neurokinin A-related peptide shows moderate affinity but lack of selectivity for all three tachykinin-binding sites in rat tissues. This non-selectivity is similar to that displayed by the molluscan tachykinin, eledoisin, which also contains an isoleucine residue in the corresponding position in the molecule.

Amino Acid Sequence↗
PubMed1991

[The effect of chronic alcohol consumption on blood pressure].

In 1984, a hypertension screening programme was carried out on 13,772 adult subjects in conjunction with a radiological tuberculosis project in the Hungarian town of Csongrád. Among other factors, the effects of a long-lasting and heavy alcohol intake on blood pressure levels were investigated. 21.4% of the men and 2.3% of women admitted to being regular alcohol consumers. Direct and significant relationships were found between the quantity of alcohol consumed and both the systolic (p less than 0.001) and diastolic (p less than 0.05) blood pressures. The prevalence of hypertension (WHO criteria) was higher in heavy drinkers (29.9%) than in abstinent subjects (20.5%, p less than 0.001). When participants were subgrouped according to age groups only the men provided sufficient data. The systolic blood pressure of heavy drinkers was elevated as compared with that of non-drinkers.

Alcohol Drinking↗
PubMed1991

Ranakinin: a novel NK1 tachykinin receptor agonist isolated with neurokinin B from the brain of the frog Rana ridibunda.

An extract of the whole brain of the frog Rana ridibunda contained high concentrations of substance P-like immunoreactivity, measured with an antiserum directed against the COOH-terminal region of mammalian substance P and neurokinin B-like immunoreactivity, measured with an antiserum directed against the NH2-terminus of neurokinin B. The primary structure of the substance P-related peptide (ranakinin) was established as: Lys-Pro-Asn-Pro-Glu-Arg-Phe-Tyr-Gly-Leu-Met-NH2. Mammalian substance P was not present in the extract. The primary structure of the neurokinin B-related peptide was established as: Asp-Met-His-Asp-Phe-Phe-Val-Gly-Leu-Met-NH2. This amino acid sequence is the same as that of mammalian neurokinin B. Ranakinin was equipotent with substance P and [Sar9,Met(O2)11]substance P in inhibiting the binding of 125I-Bolton-Hunter-[Sar9,Met(O2)11]substance P, a selective radioligand for the NK1 receptor, to binding sites in rat submandibular gland membranes (IC50 1.6 +/- 0.3 nM; n = 5). It is concluded that ranakinin is a preferred agonist for the mammalian NK1 tachykinin receptor subtype.

Amino Acid Sequence↗
PubMed1989

Hypertension screening in a Hungarian town.

In conjunction with a radiological tuberculosis project, a hypertension screening programme was carried out in 1984 on 13,772 people (74% of the eligible adult population) in the Hungarian town of Csongrád. In the younger age groups the blood pressure was found to be higher amongst men, whilst in older groups the women had higher blood pressures. By the WHO criteria, systolic hypertension was detected in one-third of the population and diastolic hypertension in one-sixth. Of the hypertensive patients detected, 34% were previously unaware of their diagnosis. The prevalence of hypertension was elevated particularly amongst obese persons and in the sub-group of physical (blue collar) workers aged over 60 years. There was a significant correlation between alcohol consumption and both systolic and diastolic blood pressures. Hypertension was found in 29.9% of heavy drinkers but in only 20.5% of moderate drinkers or total abstainers.

Adolescent↗
PubMedDate not supplied

Receptor binding profile of neuropeptide gamma and its fragments: comparison with the nonmammalian peptides carassin and ranakinin at three mammalian tachykinin receptors.

The tachykinin binding site preferences of neuropeptide gamma (NP gamma), its C-terminal fragments AcNP gamma(3-21), AcNP gamma(5-21), AcNP gamma(7-21), and AcNP gamma(9-21), other mammalian tachykinins, and the nonmammalian tachykinins ranakinin and carassin were examined in membrane binding competition studies. [125I]-Bolton-Hunter [Sar9,Met(O2)11]SP (BHSarSP), [125I]-neurokinin A (INKA) and [125I]-Bolton-Hunter scyliorhinin II (BHScyII) were used to investigate NK-1, NK-2, and NK-3 sites, in rat submandibular gland, gastric fundus, and brain, respectively. Elongation of the neurokinin A molecule does not appear to influence binding to rat tachykinin NK-1 and NK-2 binding sites. Ranakinin has affinity for the NK-1 and NK-2 site similar to that of substance P and neurokinin A, respectively, but has low affinity for the NK-3 site. Despite its structural similarities to neuropeptide gamma, carassin has only moderate affinity for rat tachykinin binding sites. Possession of an acidic residue at position 4 appears critical for binding to rat NK-2 sites.

Amino Acid Sequence↗