ChemInform Abstract: Stereospecific Synthesis of Conformationally Constrained γ-Amino Acids: New Foldamer Building Blocks That Support Helical Secondary Structure.

ChemInform ◽  
2010 ◽  
Vol 41 (10) ◽  
Author(s):  
Li Guo ◽  
Yonggui Chi ◽  
Aaron M. Almeida ◽  
Ilia A. Guzei ◽  
Brian K. Parker ◽  
...  
Keyword(s):  
Amino Acids ◽  
Secondary Structure ◽  
Building Blocks ◽  
Stereospecific Synthesis ◽  
Conformationally Constrained

scholarly journals Synthesis of new Cα-tetrasubstituted α-amino acids

2009 ◽  
Vol 5 ◽  
Author(s):  
Andreas A Grauer ◽  
Burkhard König
Keyword(s):  
Amino Acids ◽  
Secondary Structure ◽  
Aromatic Aldehydes ◽  
Building Blocks ◽  
Reaction Conditions ◽  
Peptide Backbone ◽  
Aliphatic Aldehydes ◽  
New Class ◽  
Cyclic Amino Acids

Cα-Tetrasubstituted α-amino acids are important building blocks for the synthesis of peptidemimetics with stabilized secondary structure, because of their ability to rigidify the peptide backbone. Recently our group reported a new class of cyclic Cα-tetrasubstituted tetrahydrofuran α-amino acids prepared from methionine and aromatic aldehydes. We now report the extension of this methodology to aliphatic aldehydes. Although such aldehydes are prone to give aldol products under the reaction conditions used, we were able to obtain the target cyclic amino acids in low to moderate yields and in some cases with good diastereoselectivity.

scholarly journals On the emergence of homochirality and life itself

2021 ◽  
Vol 43 (1) ◽  
pp. 4-12
Author(s):  
Jeffrey Skolnick ◽  
Mu Gao
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Hydrogen Bonding ◽  
Secondary Structure ◽  
Building Block ◽  
Building Blocks ◽  
Native State ◽  
Protein Properties ◽  
Life Itself

Many of life’s molecules including proteins are built from chiral building blocks. What drove homochiral building block selection? Simulations on demi-chiral proteins containing equal numbers of d- and l-amino acids show that they possess many modern homochiral protein properties. They have the same global folds and could do the same biochemistry, with ancient, essential functions being most prevalent. They could synthesize chiral RNA and lipids which formed vesicles. RNA eventually combined with proteins creating ribosomes for more efficient protein synthesis, and thus, life began. Increased native state stability from homochiral secondary structure hydrogen bonding helped drive proteins towards homochirality.

scholarly journals Occurrence of the d-Proline Chemotype in Enzyme Inhibitors

Symmetry ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 558 ◽  
Author(s):  
Elena Lenci ◽  
Andrea Trabocchi
Keyword(s):  
Amino Acids ◽  
Protein Interactions ◽  
Medicinal Chemistry ◽  
Enzyme Inhibitors ◽  
Proteolytic Enzymes ◽  
Building Blocks ◽  
Protein Protein Interactions ◽  
Conformationally Constrained ◽  
Biological Outcomes ◽  
Insight Into

Natural and nonnatural amino acids represent important building blocks for the development of peptidomimetic scaffolds, especially for targeting proteolytic enzymes and for addressing protein–protein interactions. Among all the different amino acids derivatives, proline is particularly relevant in chemical biology and medicinal chemistry due to its secondary structure’s inducing and stabilizing properties. Also, the pyrrolidine ring is a conformationally constrained template that can direct appendages into specific clefts of the enzyme binding site. Thus, many papers have appeared in the literature focusing on the use of proline and its derivatives as scaffolds for medicinal chemistry applications. In this review paper, an insight into the different biological outcomes of d-proline and l-proline in enzyme inhibitors is presented, especially when associated with matrix metalloprotease and metallo-β-lactamase enzymes.

CLASSIFICATIONS OF AMINO ACIDS IN PROTEINS BY THE SELF-ORGANIZING MAP

2005 ◽  
Vol 16 (10) ◽  
pp. 1609-1616 ◽  
Author(s):  
MOOKYUNG CHEON ◽  
MUYOUNG HEO ◽  
IKSOO CHANG ◽  
CHOONGRAK KIM
Keyword(s):  
Amino Acids ◽  
Secondary Structure ◽  
Protein Structures ◽  
Building Blocks ◽  
Side Chain ◽  
Self Organizing Map ◽  
Energy Parameters ◽  
Physico Chemical ◽  
Body Energy ◽  
Self Organizing

We present the clustering properties of amino acids, which are building blocks of proteins, according to their physico-chemical characters. To classify the 20 kinds of amino acids, we employ a Self-Organizing Map (SOM) analysis for the Miyazawa-Jernigan (MJ) pairwise-contact matrix, the Environment-dependent One-body energy Parameters (EOP) and the one-body energy parameters incorporating the Ramachandran angle information (EOPR) over the EOP in proteins. We provide the new result of the SOM clustering for amino acids based on the EOPR and compare that with those from the MJ and the EOP matrix. All three kinds of energy parameters capture the leading role played by the hydrophobicity and the hydrophilicity of amino acids in protein folding. Our SOM analysis generally illustrates that both the EOP and the EOPR can provide the collective clustering of amino acids by the side chain characteristics and the secondary structure information. However, EOP is better at classifying amino acids according to their side chain characteristics whereas EOPR is better with secondary structure. We show that the EOP and the EOPR matrix manifests more detailed physico-chemical classification of amino acids than those from the MJ matrix, which does not contain a local environmental information of amino acids in the protein structures.

scholarly journals Chiroptical activity of hydroxycarboxylic acids with implications for the origin of biological homochirality

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jana Bocková ◽  
Nykola C. Jones ◽  
Uwe J. Meierhenrich ◽  
Søren V. Hoffmann ◽  
Cornelia Meinert
Keyword(s):  
Amino Acids ◽  
Lactic Acid ◽  
Organic Molecules ◽  
Building Blocks ◽  
Aliphatic Chain ◽  
Monocarboxylic Acids ◽  
Hydroxycarboxylic Acids ◽  
Polarised Light ◽  
Suitable Target ◽  
Anisotropy Spectra

AbstractCircularly polarised light (CPL) interacting with interstellar organic molecules might have imparted chiral bias and hence preluded prebiotic evolution of biomolecular homochirality. The l-enrichment of extra-terrestrial amino acids in meteorites, as opposed to no detectable excess in monocarboxylic acids and amines, has previously been attributed to their intrinsic interaction with stellar CPL revealed by substantial differences in their chiroptical signals. Recent analyses of meteoritic hydroxycarboxylic acids (HCAs) – potential co-building blocks of ancestral proto-peptides – indicated a chiral bias toward the l-enantiomer of lactic acid. Here we report on novel anisotropy spectra of several HCAs using a synchrotron radiation electronic circular dichroism spectrophotometer to support the re-evaluation of chiral biomarkers of extra-terrestrial origin in the context of absolute photochirogenesis. We found that irradiation by CPL which would yield l-excess in amino acids would also yield l-excess in aliphatic chain HCAs, including lactic acid and mandelic acid, in the examined conditions. Only tartaric acid would show “unnatural” d-enrichment, which makes it a suitable target compound for further assessing the relevance of the CPL scenario.

scholarly journals Synthesis, Characterization and Evaluation of Peptide Nanostructures for Biomedical Applications

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4587
Author(s):  
Fanny d’Orlyé ◽  
Laura Trapiella-Alfonso ◽  
Camille Lescot ◽  
Marie Pinvidic ◽  
Bich-Thuy Doan ◽  
...  
Keyword(s):  
Amino Acids ◽  
Biomedical Applications ◽  
Chemical Reactivity ◽  
Physical Stability ◽  
Chemical Properties ◽  
Building Blocks ◽  
Imaging Probes ◽  
Therapeutic Molecules

There is a challenging need for the development of new alternative nanostructures that can allow the coupling and/or encapsulation of therapeutic/diagnostic molecules while reducing their toxicity and improving their circulation and in-vivo targeting. Among the new materials using natural building blocks, peptides have attracted significant interest because of their simple structure, relative chemical and physical stability, diversity of sequences and forms, their easy functionalization with (bio)molecules and the possibility of synthesizing them in large quantities. A number of them have the ability to self-assemble into nanotubes, -spheres, -vesicles or -rods under mild conditions, which opens up new applications in biology and nanomedicine due to their intrinsic biocompatibility and biodegradability as well as their surface chemical reactivity via amino- and carboxyl groups. In order to obtain nanostructures suitable for biomedical applications, the structure, size, shape and surface chemistry of these nanoplatforms must be optimized. These properties depend directly on the nature and sequence of the amino acids that constitute them. It is therefore essential to control the order in which the amino acids are introduced during the synthesis of short peptide chains and to evaluate their in-vitro and in-vivo physico-chemical properties before testing them for biomedical applications. This review therefore focuses on the synthesis, functionalization and characterization of peptide sequences that can self-assemble to form nanostructures. The synthesis in batch or with new continuous flow and microflow techniques will be described and compared in terms of amino acids sequence, purification processes, functionalization or encapsulation of targeting ligands, imaging probes as well as therapeutic molecules. Their chemical and biological characterization will be presented to evaluate their purity, toxicity, biocompatibility and biodistribution, and some therapeutic properties in vitro and in vivo. Finally, their main applications in the biomedical field will be presented so as to highlight their importance and advantages over classical nanostructures.

Sign in / Sign up

Export Citation Format

Share Document