Biomedical subjects
Publications and source records attributed to S Erhan.
A method was developed to prepare a simple, flexibilized gelatin film-based artificial skin model. The films are tough, adhere to open wounds spontaneously, are permeable to body fluids, and can release incorporated bioactive compounds over 4-5 days.
Any delivery system for bioactive molecules should have the ability to release the compound in question in a reproducible and predictable way over a certain period. For artificial skin models that are designed to enhance healing by the use of growth factors, this requirement poses another problem: the design of a delivery method that can provide a realistic assessment of the release kinetics. This means that the design should "mimic" conditions encountered in an open wound, i.e., only a certain part of the film can face the wound, from which it can absorb wound fluid that will dissolve the incorporated bioactive molecule and bring it to the open wound. Such a system has been developed and the release of 125I-labelled insulin, incorporated into flexibilized gelatin films, has been determined. The details of this study follow.
Inability to increase the yield of reaction between 2,4 dihydroxybenzaldehyde and gelatin beyond 55 and 60% has led to an extensive investigation of reductive alkylation with free lysine. Even with free lysine, the extent of reaction was about 60%. Since this could be attributed to the electron donation by the phenolic hydroxyls, reductive alkylation was performed between o-, m-, and p-nitrobenzaldehydes and free lysine; o- and m-nitrobenzaldehyde were ineffective in increasing the yield while with p-nitrobenzaldehyde a yield of 72% was achieved. The unreacted 28% of the lysines are susceptible to epichlorohydrin. These results suggest that the slow, reversible first step in reductive alkylation, the formation of the Schiff's base, is responsible for the low yield.
A method has been developed which allows the breakdown of an amino-acid sequence of proteins into overlapping di-, tripeptides, etc. The frequency of their distribution provides very convincing evidence that these sequences are non-random. These peptides have been demonstrated to be capable of being used as an objective key for the classification of organisms, and of proteins. It is also believed that they can be useful in increasing the accuracy of the prediction of protein folding.
A new method, based on the frequency distribution of amino-acid pairs, is developed to represent proteins. The method can accommodate and convey all of the chemical and many of the physical properties of proteins. It also lends itself to classification of organisms from which a protein is obtained (Erhan, 1978) and also to classification of protein families (Erhan, in preparation).
A method is developed to classify proteins by establishing their familial identity based on the presence and the absence of characteristic signature dipeptides. It is hoped that this method will lead to the establishment of a theoretical basis for the determination of interrelationships among proteins.
A mechanism is proposed for the formation of Ebg-evolved beta galactosidase-of E. coli based on the following assumptions: 1. In the presence of lactose, certain proteins being translated bind to their m-RNA-ribosome complexes; 2. This binding interferes with the release of m-RNA from the bacterial chromosome, marking the gene; 3. Thereupon a cytosine specific methylase and methyl cytosine deaminase pair, modify - mutate - the marked gene; 4. The result, after five or so mutations, is a new gene capable of coding for a different protein which can split lactose; 5. I propose that this enzyme pair has evolved to produce mutations internally, when need arises, as is the case here; 6. This may be a general mechanism through which drug resistance and detoxification of a novel chemical, could be achieved in bacteria; 7. All of these ideas are experimentally testable.
Although it is one of the oldest of modern disciplines, systematics has always been a science practised in a highly personalised and subjective way because of the need to rely on morphological characteristics of the living organisms, as well as the fossil remains, for their classification. Recent studies on the amino acid nearest neighbours, however, enable one to have an objective key for classifying organisms as well as their relationships.
The effect of random mutations of five identical pentapeptides that have been inserted arbitrarily along a 100 amino acid-long protein chain has been studied by computer simulation. The method used was the application of mutation probability matrix for 2 PAMs of Dayhoff (1972) repeatedly to obtain the desired length of time. The results indicated that, given sufficient length of time, even the identical peptides could become drastically altered and in order to recognise them as stemming from the same origin one has to use reasonable statistical significance thresholds.
Significant amino acid homologies were found between beta-galactosidase fragments and lac repressor of E. coli using a sliding match according to Greller and Erhan (1974). Since both of these proteins can recognise and bind galactose moiety, we propose that the homologous regions represetn galactose binding site(s) on both proteins. Possible application of homology studies to problems of protein and nucleic acid chemistry is also discussed.
When the primary structure of bovine trypsinogen is searched for the existence of regularities, according to Greller & Erhan (1974), one finds eight pairs of peptides, arranged in a symmetrical pattern along the molecule. These peptides cover 49% of the length of the molecule-112 of the 227 amino acids-and each pair folds in a similar way. This observation is in agreement with the observation that "Trypsin folds into two halves, each of which contains a pseudo-cylindrical arrangement of hydrogen bonds...", Stroud et al. (1971). Thus the above mentioned method is capable not only of detecting regulatities along the primary structure but also of predicting the folding of a protein.
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Both E. coli and calf thymus DNA polymerase can be phosphorylated by cAMP-dependent protein kinase and phosphorylation appears to stimulate the DNA polymerase reaction. Conversely, dephosphorylation of the polymerase molecule, by a protein phosphatase, inhibits the polymerase reaction.
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