Protein phosphorylation is a critical regulatory strategy. New tools are necessary which may be used to interrogate and are responsive to the activities of protein kinases and phosphatases. We have used protein design to develop a protein motif, termed a protein kinase-inducible domain, whose structure is dependent on its phosphorylation state. Based on an EF hand calcium-binding loop, the key design element is the replacement of a structurally critical Glu residue, which binds metal in a bidentate manner, with a serine residue, which is expected to bind metal tightly when phosphorylated but poorly when not phosphorylated. The design comprises an EF hand consensus sequence, a tryptophan at residue 7 to sensitize lanthanide luminescence, and the recognition sequence of a serine/threonine kinase. Designed peptides, which contain minimal substrate recognition motifs of the protein kinases PKA, PKC, or the MAP kinase Erk, form complexes with Tb3+ when phosphorylated, showing strong Tb3+ luminescence emission at 544 nm, but show weak luminescence when not phosphorylated. The change in fluorescence on phosphorylation is comparable to or greater than that observed in described kinase sensors. Site-specific lanthanide binding was confirmed by NMR with diamagnetic and paramagnetic metals. The kinase-inducible domain peptides comprise an expressible sequence, potentially enabling their use as genetically encoded tags of protein kinase activity. The motif is general and potentially applicable to the majority of serine/threonine kinases.

Arginine residues are broadly employed for specific biomolecular recognition, including in protein-protein, protein-DNA, and protein-RNA interactions. Arginine recognition commonly exploits the potential for bidentate electrostatic and hydrogen-bonding interactions. However, in arginine residues, the guanidinium functional group is located at the terminus of a flexible hydrocarbon side chain, which lacks the functionality to contribute to specific arginine-mediated recognition and may entropically disfavor binding. In order to enhance the potential for specificity and affinity in arginine-mediated molecular recognition, we have developed an approach to the synthesis of peptides that incorporates an α-guanidino acid as a novel arginine mimetic. α–Guanidino acids, derived from α-amino acids, with guanylation of the amino group, were incorporated stereospecifically into peptides on solid phase via coupling of an Fmoc amino acid to diaminoproprionic acid (Dap), Fmoc deprotection, guanylation of the amine on solid phase, and deprotection, generating a peptide containing an α-functionalized arginine mimetic. This approach was examined via the incorporation of arginine mimetics into ligands for the Src, Grb, and Crk SH3 domains at the site of the key recognition arginine. Protein binding was examined for peptides containing guanidino acids derived from Gly, l-Val, l-Phe, l-Trp, d-Val, d-Phe, and d-Trp. We demonstrate that paralog specificity and target site affinity may be modulated via the use of α-guanidino acid-derived arginine mimetics, generating peptides that exhibit enhanced Src specificity via selection against Grb and peptides that reverse the specificity of the native peptide ligand, with enhancements in Src target specificity of up to 15-fold (1.6 kcal/mol).

To introduce chirality and functional groups adjacent to guanidiniums to modulate specificity and affinity in recognition, N,N'-bis(Boc)-alpha-guanidino acids were synthesized from alpha-amino acid methyl esters. Protected alpha-guanidino acids coupled to cyclohexylamine and trans-1,4-diaminocyclohexane in good yield and with retention of stereochemistry. Boc deprotection was conducted under mild acidic conditions (0.5 M HCl/EtOAc) to minimize epimerization. The deprotected guanidinium is configurationally stable under more acidic conditions. This approach represents a practical, convergent, stereospecific methodology to introduce chiral alpha-substituted guanidinium groups into molecules.

In this review article attention is put towards the common India medicinal plant, Wheat grass that has been put into use as a part of Ayurvedic medicine. Wheat grass juice is an effective healer because it contains all mineral known to man and vitamins A, B-Complex, C E and K. It is extremely rich in protein and contains 17 amino acids, the building blocks of protein. It contains enzymes that decomposes superoxide radicals in the body. Wheat grass seems to have positive effects on blood sugar levels. Wheat grass juice seems to increase strength and endure and renew health. Wheat grass juice consumption is seen both in urban and rural diet style. Thus, it is necessary to study and research the relevant medicinal effect of these active components found in young wheat grass on both normal and COVID effected patients to fight the diseases by enhancing the function of immune system to ward off infection and diseases.

Guanidine derivatives P 0510 Convergent and Stereospecific Synthesis of Molecules Containing α-Functionalized Guanidiniums via α-Guanidino Acids. -During Boc deprotection with 0.5M HCl minimal epimerization takes place. -(BALAKRISHNAN, S.; ZHAO, C.; ZONDLO*, N. J.; J. Org. Chem. 72 (2007) 25, 9834-9837; Dep. Chem. Biochem., Univ. Del., Newark, DE 19716, USA; Eng.) -Jannicke