scholarly journals Asymmetric Synthesis of Tetrasubstituted α-Aminophosphonic Acid Derivatives

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3202
Author(s):  
Aitor Maestro ◽  
Xabier del Corte ◽  
Adrián López-Francés ◽  
Edorta Martínez de Marigorta ◽  
Francisco Palacios ◽  
...  
Keyword(s):  
Amino Acids ◽  
Biological Activity ◽  
Absolute Configuration ◽  
Strong Dependence ◽  
Structural Similarity ◽  
Optically Active ◽  
Biologically Active ◽  
Chiral Molecules ◽  
Aminophosphonic Acid ◽  
The Past

Due to their structural similarity with natural α-amino acids, α-aminophosphonic acid derivatives are known biologically active molecules. In view of the relevance of tetrasubstituted carbons in nature and medicine and the strong dependence of the biological activity of chiral molecules into their absolute configuration, the synthesis of α-aminophosphonates bearing tetrasubstituted carbons in an asymmetric fashion has grown in interest in the past few decades. In the following lines, the existing literatures for the synthesis of optically active tetrasubstituted α-aminophosphonates are summarized, comprising diastereoselective and enantioselective approaches.

scholarly journals Transforming growth factor alpha: mutation of aspartic acid 47 and leucine 48 results in different biological activities.

1988 ◽  
Vol 8 (3) ◽  
pp. 1247-1252 ◽  
Author(s):  
E Lazar ◽  
S Watanabe ◽  
S Dalton ◽  
M B Sporn
Keyword(s):  
Amino Acids ◽  
Biological Activity ◽  
Amino Acid ◽  
Growth Factor ◽  
Aspartic Acid ◽  
Transforming Growth Factor ◽  
Biologically Active ◽  
Single Amino Acid ◽  
Transforming Growth Factor Alpha ◽  
Factor Alpha

To study the relationship between the primary structure of transforming growth factor alpha (TGF-alpha) and some of its functional properties (competition with epidermal growth factor (EGF) for binding to the EGF receptor and induction of anchorage-independent growth), we introduced single amino acid mutations into the sequence for the fully processed, 50-amino-acid human TGF-alpha. The wild-type and mutant proteins were expressed in a vector by using a yeast alpha mating pheromone promoter. Mutations of two amino acids that are conserved in the family of the EGF-like peptides and are located in the carboxy-terminal part of TGF-alpha resulted in different biological effects. When aspartic acid 47 was mutated to alanine or asparagine, biological activity was retained; in contrast, substitutions of this residue with serine or glutamic acid generated mutants with reduced binding and colony-forming capacities. When leucine 48 was mutated to alanine, a complete loss of binding and colony-forming abilities resulted; mutation of leucine 48 to isoleucine or methionine resulted in very low activities. Our data suggest that these two adjacent conserved amino acids in positions 47 and 48 play different roles in defining the structure and/or biological activity of TGF-alpha and that the carboxy terminus of TGF-alpha is involved in interactions with cellular TGF-alpha receptors. The side chain of leucine 48 appears to be crucial either indirectly in determining the biologically active conformation of TGF-alpha or directly in the molecular recognition of TGF-alpha by its receptor.

scholarly journals Biologically active LIL proteins built with minimal chemical diversity

2015 ◽  
Vol 112 (34) ◽  
pp. E4717-E4725 ◽  
Author(s):  
Erin N. Heim ◽  
Jez L. Marston ◽  
Ross S. Federman ◽  
Anne P. B. Edwards ◽  
Alexander G. Karabadzhak ◽  
...  
Keyword(s):  
Amino Acids ◽  
Biological Activity ◽  
Transmembrane Domain ◽  
Transmembrane Proteins ◽  
Chemical Diversity ◽  
Biologically Active ◽  
Cellular Context ◽  
Hydrophobic Amino Acids ◽  
Β Receptor ◽  
Specific Sequences

We have constructed 26-amino acid transmembrane proteins that specifically transform cells but consist of only two different amino acids. Most proteins are long polymers of amino acids with 20 or more chemically distinct side-chains. The artificial transmembrane proteins reported here are the simplest known proteins with specific biological activity, consisting solely of an initiating methionine followed by specific sequences of leucines and isoleucines, two hydrophobic amino acids that differ only by the position of a methyl group. We designate these proteins containing leucine (L) and isoleucine (I) as LIL proteins. These proteins functionally interact with the transmembrane domain of the platelet-derived growth factor β-receptor and specifically activate the receptor to transform cells. Complete mutagenesis of these proteins identified individual amino acids required for activity, and a protein consisting solely of leucines, except for a single isoleucine at a particular position, transformed cells. These surprisingly simple proteins define the minimal chemical diversity sufficient to construct proteins with specific biological activity and change our view of what can constitute an active protein in a cellular context.

scholarly journals Monoterpenes as a renewable source of biologically active compounds

2017 ◽  
Vol 89 (8) ◽  
pp. 1105-1117 ◽  
Author(s):  
Nariman F. Salakhutdinov ◽  
Konstantin P. Volcho ◽  
Olga I. Yarovaya
Keyword(s):  
Biological Activity ◽  
Absolute Configuration ◽  
Biologically Active Compounds ◽  
Biologically Active ◽  
Great Promise ◽  
Active Compounds ◽  
Renewable Source ◽  
The Creation ◽  
Anti Inflammatory

AbstractMonoterpenes and their derivatives play an important role in the creation of new biologically active compounds including drugs. The review focuses on the data on various types of biological activity exhibited by monoterpenes and their derivatives, including analgesic, anti-inflammatory, anticonvulsant, antidepressant, anti-Alzheimer, anti-Parkinsonian, antiviral, and antibacterial (anti-tuberculosis) effects. Searching for novel potential drugs among monoterpene derivatives shows great promise for treating various pathologies. Special attention is paid to the effect of absolute configuration of monoterpenes and monoterpenoids on their activity.

ChemInform Abstract: Synthesis of New Racemic and Optically Active N-Phosphonoalkyl Bicyclic β-Amino Acids via the Kabachnik-Fields Reaction as Potential Biologically Active Compounds.

ChemInform ◽  
2012 ◽  
Vol 43 (30) ◽  
pp. no-no
Author(s):  
Petar T. Todorov ◽  
Nikola D. Pavlov ◽  
Boris L. Shivachev ◽  
Rosica N. Petrova ◽  
Jean Martinez ◽  
...  
Keyword(s):  
Amino Acids ◽  
Optically Active ◽  
Biologically Active Compounds ◽  
Biologically Active ◽  
Active Compounds

scholarly journals Cleavage of K-FGF produces a truncated molecule with increased biological activity and receptor binding affinity.

1993 ◽  
Vol 121 (3) ◽  
pp. 705-713 ◽  
Author(s):  
P Bellosta ◽  
D Talarico ◽  
D Rogers ◽  
C Basilico
Keyword(s):  
Amino Acids ◽  
Biological Activity ◽  
Growth Factor ◽  
Binding Affinity ◽  
Receptor Binding ◽  
Biologically Active ◽  
Heparin Binding ◽  
Wild Type ◽  
Mammalian Expression

The K-FGF/HST (FGF-4) growth factor is a member of the FGF family which is efficiently secreted and contains a single N-linked glycosylation signal. To study the role of glycosylation in the secretion of K-FGF, we mutated the human K-fgf cDNA to eliminate the glycosylation signal and the mutated cDNA was cloned into a mammalian expression vector. Studies of immunoprecipitation from the conditioned medium of cells expressing this plasmid revealed that the lack of glycosylation did not impair secretion, however the unglycosylated protein was immediately cleaved into two NH2-terminally truncated peptides of 13 and 15 kD, which appeared to be more biologically active than the wild-type protein. These two proteins also showed higher heparin binding affinity than that of wt K-FGF. We have expressed in bacteria the larger of these two proteins (K140), in which the NH2-terminal 36 amino acids present in the mature form of K-FGF have been deleted. Mitogenicity assays on several cell lines showed that purified recombinant K140 had approximately five times higher biological activity than wild-type recombinant K-FGF. Studies of receptor binding showed that K140 had higher affinity than wt K-FGF for two of the four members of FGF receptor's family, specifically for FGFR-1 (flg) and FGFR-2 (bek). K140 also had increased heparin binding ability, but this property does not appear to be responsible for the increased affinity for FGF receptors. Thus removal of the NH2-terminal 36 amino acids from the mature K-FGF produces growth factor molecules with an altered conformation, resulting in higher heparin affinity, and more efficient binding to FGF receptors. Although it is not clear whether cleavage of K-FGF to generate K140 occurs in vivo, this could represent a novel mechanism of modulation of growth factor activity.

Transforming growth factor alpha: mutation of aspartic acid 47 and leucine 48 results in different biological activities

1988 ◽  
Vol 8 (3) ◽  
pp. 1247-1252
Author(s):  
E Lazar ◽  
S Watanabe ◽  
S Dalton ◽  
M B Sporn
Keyword(s):  
Amino Acids ◽  
Biological Activity ◽  
Amino Acid ◽  
Growth Factor ◽  
Aspartic Acid ◽  
Transforming Growth Factor ◽  
Biologically Active ◽  
Single Amino Acid ◽  
Transforming Growth Factor Alpha ◽  
Factor Alpha

To study the relationship between the primary structure of transforming growth factor alpha (TGF-alpha) and some of its functional properties (competition with epidermal growth factor (EGF) for binding to the EGF receptor and induction of anchorage-independent growth), we introduced single amino acid mutations into the sequence for the fully processed, 50-amino-acid human TGF-alpha. The wild-type and mutant proteins were expressed in a vector by using a yeast alpha mating pheromone promoter. Mutations of two amino acids that are conserved in the family of the EGF-like peptides and are located in the carboxy-terminal part of TGF-alpha resulted in different biological effects. When aspartic acid 47 was mutated to alanine or asparagine, biological activity was retained; in contrast, substitutions of this residue with serine or glutamic acid generated mutants with reduced binding and colony-forming capacities. When leucine 48 was mutated to alanine, a complete loss of binding and colony-forming abilities resulted; mutation of leucine 48 to isoleucine or methionine resulted in very low activities. Our data suggest that these two adjacent conserved amino acids in positions 47 and 48 play different roles in defining the structure and/or biological activity of TGF-alpha and that the carboxy terminus of TGF-alpha is involved in interactions with cellular TGF-alpha receptors. The side chain of leucine 48 appears to be crucial either indirectly in determining the biologically active conformation of TGF-alpha or directly in the molecular recognition of TGF-alpha by its receptor.

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