Action of thiazolidine-2-carboxylic acid, a proline analog, on protein synthesizing systems

Busiello, V.; Girolamo, M. Di; Cini, Chiara; Marco, C. De

doi:10.1016/0005-2787(79)90228-4

Cited by 16 publications

(7 citation statements)

References 7 publications

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“…Due to structural similarity to proline, these compounds can probably substitute proline in collagen biosynthesis. It has been also documented that they impair proline oxidation by POX [ 34 – 36 ]. Based on cytotoxicity of both compounds, we selected concentration 10 mM of FA and 5 mM of TA.…”

Section: Resultsmentioning

confidence: 99%

Exogenous proline stimulates type I collagen and HIF-1α expression and the process is attenuated by glutamine in human skin fibroblasts

et al. 2017

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Abundance of proline (Pro) in collagen molecule led us to investigate whether Pro supply affects collagen biosynthesis in human skin fibroblasts. Treatment of the cells with milimolar concentrations (5 and 10 mM) of Pro for 24 and 48 h contributed to increase in α1 subunit of collagen type I (COL1A1) expression in both cells and culture medium. However, the effect was more pronounced in glutamine-free medium. In such condition, Pro induced collagen expression by about twofold in the cells, while in the medium only by about 30% during 24 h incubation, compared to control. In the presence of glutamine (Gln), exogenous Pro stimulated intracellular collagen expression only by about 30% during 24 h of fibroblasts incubation, and it was not accompanied by adequate increase of collagen secretion into medium. Gln alone stimulated the processes by about 2–3 fold during the course of the experiment. Pro-dependent increase in collagen expression in Gln-free medium was accompanied by increase in prolidase activity and expression of pAkt. In both Gln-free medium and Gln-supplemented medium, Pro induced expression of p53 and HIF-1α. The data suggest that availability of Gln, as a substrate for Pro biosynthesis, determine the utilization of exogenous Pro for the collagen biosynthesis.

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Section: Resultsmentioning

confidence: 99%

Exogenous proline stimulates type I collagen and HIF-1α expression and the process is attenuated by glutamine in human skin fibroblasts

et al. 2017

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“…All four proline analogs: thiazolidine-2-carboxylic acid (N21) [45] thiazolidine-4-carboxylic acid (N22) [46], 3,4-dehydro proline (N23) [47], [48], and l- azetidine-2-carboxylic acid (N24) [1], [49], were excellent substrates for the translation apparatus.…”

Section: Resultsmentioning

confidence: 99%

An Expanded Set of Amino Acid Analogs for the Ribosomal Translation of Unnatural Peptides

et al. 2007

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BackgroundThe application of in vitro translation to the synthesis of unnatural peptides may allow the production of extremely large libraries of highly modified peptides, which are a potential source of lead compounds in the search for new pharmaceutical agents. The specificity of the translation apparatus, however, limits the diversity of unnatural amino acids that can be incorporated into peptides by ribosomal translation. We have previously shown that over 90 unnatural amino acids can be enzymatically loaded onto tRNA.Methodology/Principal FindingsWe have now used a competition assay to assess the efficiency of tRNA-aminoacylation of these analogs. We have also used a series of peptide translation assays to measure the efficiency with which these analogs are incorporated into peptides. The translation apparatus tolerates most side chain derivatives, a few α,α disubstituted, N-methyl and α-hydroxy derivatives, but no β-amino acids. We show that over 50 unnatural amino acids can be incorporated into peptides by ribosomal translation. Using a set of analogs that are efficiently charged and translated we were able to prepare individual peptides containing up to 13 different unnatural amino acids.Conclusions/SignificanceOur results demonstrate that a diverse array of unnatural building blocks can be translationally incorporated into peptides. These building blocks provide new opportunities for in vitro selections with highly modified drug-like peptides.

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“…Such differences may be important in the efficiency of steric interactions and thus affect the efficiency of the reversion event. Both analogs are competitive inhibitors of proline (4). It is unclear why these analogs do not inhibit growth, since thiazolidine-2-carboxylic acid prevents protein elongation.…”

Section: Discussionmentioning

confidence: 99%

Proline Reverses the Abnormal Phenotypes of Colletotrichum trifolii Associated with Expression of Endogenous Constitutively Active Ras

Memmott

Dickman

2002

Appl Environ Microbiol

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Colletotrichum trifolii is the causative organism of alfalfa anthracnose. We previously cloned and characterized the small prototypical G protein, Ras, of C. trifolii, which is involved in the signaling pathways that mediate interaction between the pathogen and its host. Transformants expressing constitutively active forms of Ras have growth medium-dependent phenotypes. In nutrient-rich media (e.g., yeast extract and peptone), the phenotype of the transformants was indistinguishable from that of the wild type. However, during nutrient starvation, the transformants lose polarity, have distended hyphae, and fail to sporulate and produce appressoria. Since peptone caused the phenotype to revert, amino acids were tested singly and in combination to identify the responsible amino acid(s). We found that 1.6 mM proline in the medium reverses the constitutively active Ras phenotype.Pathogenic development of filamentous fungi requires perception of the environment and response to appropriate cues. In a few cases, such signals have been identified, but the responsible pathways have not been worked out. Physical signals include plant surface topography, hydrophobicity, and rigidity (9,14,26). These physical signals generally are associated with conidial adhesion and appressorium differentiation. Chemical signals revolve around nutrient status, such as starvation or nitrogen deficiency (11,15,16). In all cases, perception of the appropriate stimulus triggers signals that eventually alter gene expression, producing the desired cellular response. Identification of the signals and the response pathways is important for understanding the underlying mechanisms responsible for fungal development, as well as suggesting targets for interference when such pathways are required for effective pathogenesis.Colletotrichum trifolii is an important fungal pathogen of alfalfa which causes anthracnose (8). The infection process relies on a tightly coordinated series of developmental transitions that begins with spore attachment to the plant surface, appressorium formation, penetration of the plant cuticle and cell wall, acquisition of nutrients from plant tissue, and the production of asexual spores in acervuli (8).Recently, we found that constitutively activated forms of Ras, the prototypical member of the superfamily of small G proteins, when expressed in C. trifolii yielded a nutrient-dependent response. The activated form of Ras was made by sitedirected mutagenesis that substituted either valine for glycine at position 17 or leucine for glutamine at position 66. Both of these amino acid changes inhibit the activity of the GTPaseactivating proteins that hydrolyze the GTP-bound active Ras to form the inactive GDP-bound form. Such inhibition ensures that Ras remains in the activated GTP-bound state and is a common mutation found in mammalian tumors.The nutrient-dependent response of active Ras when grown on minimal medium was phenotypically expressed as aberrant hyphal morphology, virtually no conidiation, and failure to produce appressori...

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Action of thiazolidine-2-carboxylic acid, a proline analog, on protein synthesizing systems

Cited by 16 publications

References 7 publications

Exogenous proline stimulates type I collagen and HIF-1α expression and the process is attenuated by glutamine in human skin fibroblasts

Exogenous proline stimulates type I collagen and HIF-1α expression and the process is attenuated by glutamine in human skin fibroblasts

An Expanded Set of Amino Acid Analogs for the Ribosomal Translation of Unnatural Peptides

Proline Reverses the Abnormal Phenotypes of Colletotrichum trifolii Associated with Expression of Endogenous Constitutively Active Ras

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