Peptide name : cyclic dipeptide - 2b

Source/Organism : Synthetic

Linear/Cyclic : Cyclic

Chirality : L

Peptide length: 2

C-terminal modification: Cyclic

N-terminal modification : Cyclized

Non-natural peptide information: L-7dimethylallyl at Trp

Assay type : MTT assay

Assay time : 72-h

Activity : IC50 = 45.6 µM

Cell line : MCF-7

Cancer type : Breast Cancer

Other activity : Anticancer

Amino acid composition bar chart :

Molecular mass : 275.3031 Dalton

Aliphatic index : 0.5

Instability index : -70.15

Hydrophobicity (GRAVY) : 0.45

Isoelectric point : 5.525

Charge (pH 7) : -0.2399

Aromaticity : 50

Molar extinction coefficient (cysteine, cystine): (0, 0)

Hydrophobic/hydrophilic ratio : infinite

hydrophobic moment : -0.606

Missing amino acid : C,D,E,F,G,H,I,K,L,M,N,P,Q,R,S,T,V,Y

Most occurring amino acid : W

Most occurring amino acid frequency : 1

Least occurring amino acid : W

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (50, 0, 50)

SMILES Notation: C[C@H](NC(=O)[C@@H](N)Cc1c[nH]c2ccccc12)C(=O)O

1 : Liu R, et al. C7-Prenylation of Tryptophan-Containing Cyclic Dipeptides by 7-Dimethylallyl Tryptophan Synthase Significantly Increases the Anticancer and Antimicrobial Activities. Molecules. 2020; 25:(unknown pages). doi: 10.3390/molecules25163676

Paper title : C7-Prenylation of Tryptophan-Containing Cyclic Dipeptides by 7-Dimethylallyl Tryptophan Synthase Significantly Increases the Anticancer and Antimicrobial Activities.

Doi : https://doi.org/10.3390/molecules25163676

Abstract : Prenylated natural products have interesting pharmacological properties and prenylation reactions play crucial roles in controlling the activities of biomolecules. They are difficult to synthesize chemically, but enzymatic synthesis production is a desirable pathway. Cyclic dipeptide prenyltransferase catalyzes the regioselective Friedel-Crafts alkylation of tryptophan-containing cyclic dipeptides. This class of enzymes, which belongs to the dimethylallyl tryptophan synthase superfamily, is known to be flexible to aromatic prenyl receptors, while mostly retaining its typical regioselectivity. In this study, seven tryptophan-containing cyclic dipeptides 1a-7a were converted to their C7-regularly prenylated derivatives 1b-7b in the presence of dimethylallyl diphosphate (DMAPP) by using the purified 7-dimethylallyl tryptophan synthase (7-DMATS) as catalyst. The HPLC analysis of the incubation mixture and the NMR analysis of the separated products showed that the stereochemical structure of the substrate had a great influence on their acceptance by 7-DMATS. Determination of the kinetic parameters proved that cyclo-l-Trp-Gly (1a) consisting of a tryptophanyl and glycine was accepted as the best substrate with a K_M value of 169.7 μM and a turnover number of 0.1307 s-1. Furthermore, docking studies simulated the prenyl transfer reaction of 7-DMATS and it could be concluded that the highest affinity between 7-DMATS and 1a. Preliminary results have been clearly shown that prenylation at C7 led to a significant increase of the anticancer and antimicrobial activities of the prenylated derivatives 1b-7b in all the activity test experiment, especially the prenylated product 4b.