Does the cis/trans configuration of peptide bonds in bioactive tripeptides play a role in ACE-1 enzyme inhibition?

Figures & data

Figure 1 Different cis/trans configurations of the peptide bond.

Notes: (A) Peptide bonds values (ω1 and ω2) in IPP and VPP are 180° and they are both in trans configuration. (B) The first peptide bond (ω1) in IPP has 0° and the second (ω2) has 180° values and they are in cis and trans configuration, respectively. The first peptide bond (ω1) in VPP has 180° and the second (ω2) has 0° values and they are in trans and cis configuration, respectively.
Abbreviations: IPP, isoleucine-proline-proline; VPP, valine-proline-proline.

Figure 2 Different cis/trans configurations of IPP.

Notes: Different cis/trans configurations of the isoleucine-proline-proline are shown in global energy minimum structures. The shortest distances between carbonyl oxygens are provided. Blue color indicates nitrogen and red color oxygen atoms. Different peptide bond configurations of IPP are sorted by energy, from smallest to largest.
Abbreviation: IPP, isoleucine-proline-proline.

Figure 3 Geometric isomers and omega values IPP and VPP

Notes: Geometric isomers and omega values for IPP were ω1 =−42 and ω2 =−7, respectively. Geometric isomers and omega values for VPP were ω1 =−99 and ω2 =84 for VPP, respectively. These values were as predicted in the angiotensin-converting enzyme 1.
Abbreviations: IPP, isoleucine-proline-proline; VPP, valine-proline-proline.

Figure 4 Angiotensin-converting enzyme 1 activity from HUVEC lysate.

Notes: Angiotensin-converting enzyme 1 activity from HUVEC lysate incubated for 60 minutes with/without IPP or VPP peptides. Captopril was used as a reference inhibitor. Mean ± SEM, n=2–4, from duplicate measurements. **P<0.01; ***P<0.001 versus control.
Abbreviations: HUVEC, human umbilical vein endothelial cells; IPP, isoleucine-proline-proline; VPP, valine-proline-proline; SEM, standard error of mean.

Figure 5 Tripeptide IPP in active site of ACE-1.

Notes: Tripeptide IPP with omega values of ω1 =−42 and ω2 =−7 in active site of ACE-1. Autodock flexible residues are labeled, as are zinc (green) and its two histidine (383, 387) and glutamine (384) ligand residues.
Abbreviations: IPP, isoleucine-proline-proline; ACE-1, angiotensin-converting enzyme 1.