Amide Bond Activation of Biological Molecules

Abstract

Amide bonds are the most prevalent structures found in organic molecules and various biomolecules such as peptides, proteins, DNA, and RNA. The unique feature of amide bonds is their ability to form resonating structures, thus, they are highly stable and adopt particular three-dimensional structures, which, in turn, are responsible for their functions. The main focus of this review article is to report the methodologies for the activation of the unactivated amide bonds present in biomolecules, which includes the enzymatic approach, metal complexes, and non-metal based methods. This article also discusses some of the applications of amide bond activation approaches in the sequencing of proteins and the synthesis of peptide acids, esters, amides, and thioesters.

Keywords: amide bond resonance; catalysts; enzymes; metal complexes; peptide bond cleavage; twisted amides.

Figure 1

Classical amide bond resonance.

Figure 2

Twisted amides for activation of amide bonds.

Figure 3

General pathway of serine proteases directed amide bond hydrolysis.

Figure 4

Thermolysin Mechanistic pathway.

Figure 5

Mechanisms of carboxypeptidase A.

Figure 6

Glycosylation pathway.

Figure 7

Mechanistic pathway of Pnc1 for hydrolysis of nicotinamide.

Figure 8

Flavoenzyme-mediated hydrolysis of amide bond.

Figure 9

Antibody Fab catalyzed primary amide bond hydrolysis.

Figure 10

RNA catalyzed amide bond cleavage.

Figure 11

Metal-assisted peptide bond hydrolysis.

Figure 12

Peptide hydrolysis catalyzed by a polyoxometalate complex.

Figure 13

Oxomolybdate(VI) catalyzed cleavage of peptide bonds.

Figure 14

Co(III) Complex catalyzed peptide hydrolysis.

Figure 15

Mo catalyzed peptide hydrolysis.

Figure 16

Pd and Pt complexes for activation of amide bonds.

Figure 17

Pd(II) aqua dimers.

Figure 18

Hydrolytic reactions of Pt complexes.

Figure 19

Hydrolytic reactions of Pd and Pt complexes.

Figure 20

[Pd(dtco)(H₂O)₂]²⁺ mediated hydrolysis of amide bond.

Figure 21

[Pd(H₂O)₄]²⁺ mediated hydrolysis of amide bond.

Figure 22

Pd triggered pH dependent hydrolysis of amide bond.

Figure 23

Cis/Trans conformations of Pd complexes.

Figure 24

pH selective Pd catalyst for the hydrolysis.

Figure 25

Acidic hydrolysis of amide bonds.

Figure 26

β-Cyclodextrin Pd-complex.

Figure 27

Artificial metal complexes with different numbers of metal centers.

Figure 28

Aldehyde pendant mediated cleavage of peptide bonds.

Figure 29

Catalyst design for protein cleavage.

Figure 30

Mechanism of Co(III)-metal complexes.

Figure 31

Metal-assisted catalyst for PDF.

Figure 32

Metal complexes for the cleavage of amyloidgenic peptides.

Figure 33

Cu complexes for activation of amide bonds.

Figure 34

Non lewis acid mediated N, O Acyl rearrangement.

Figure 35

N, O Acyl rearrangement.

Figure 36

Edman’s degradation approach for cleavage of peptide bonds.

Figure 37

Cyanogen bromide for selective cleavage at Met.

Figure 38

2-nitro-5-thiocyano benzoic acid selective cleavage at Cys.

Figure 39

Iodosobenzoic acid for hydrolysis.

Figure 40

TBC for selective cleavage at Trp residue.

Figure 41

N-amidination strategy.

Figure 42

N-amidination strategy with N-terminal cysteine.

Figure 43

Hydrogen peroxide responsive probes.

Figure 44

Glutamic acid selective activation of peptide bonds.

Figure 45

Asparagine selective cleavage of peptide bonds.

Figure 46

Cyclic urethane mediated activation of peptide bond.

Figure 47

Pyroglutamyl imide mediated activation of peptide bond.

Figure 48

Cyclic urethane mediated synthesis of C-terminal peptides.

Figure 49

Cyclic urethane for cleavage of cyclic peptides.

Figure 50

Synthesis of rotaxane from lasso peptide.

Figure 51

Intein-inspired amide bond cleavage.

Figure 52

Serine selective aerobic cleavage of peptide bonds.

Figure 53

Oxazolinium species formation.

Figure 54

Hydrazinolysis for the cleavage of peptide bonds.

Figure 55

N-methylcysteinyl peptide cleavage.

Figure 56

N-Me Aib mediated amide bond cleavage.