Two commonly used modifications of native peptides to increase peptide permeability through the cell membrane to target intracellular substrates are myristic acid conjugated peptides (MYR) and transactivating conjugated peptides (TAT). However, there is limited literature comparing the effects of these two types of modified peptides in the same bioassay. The objective of this mini-review is to compare the effects of MYR- and TAT-conjugated peptides in two bioassays: 1) Myocardial ischemia-reperfusion injury (I/R) in isolated perfused rat hearts using a mitochondrial fission peptide inhibitor, P110; 2) N-Formyl-L-Methionyl-L-Leucyl-L-Phenylalanine (fMLP)-induced superoxide (SO) release from isolated rat neutrophils using a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase peptide assembly inhibitor, Nox2ds. MYR-conjugated P110 (1 µM) exerted sustained improvement in post-reperfused cardiac function combined with reduced infarct size compared to TAT-conjugated P110 (1 µM) or native P110 peptide (1 µM) in hearts subjected to I(30 min)/R(90 min). Nox2ds data suggested that MYR-conjugated Nox2ds peptide exerted more potent effects and better permeability through the cell membrane to attenuate fMLP-induced SO release from rat neutrophils when compared to TAT-conjugated Nox2ds peptide. However, further metabolism studies are needed to determine peptide half-life between the MYR- and TAT-conjugated peptides to corroborate the pharmacodynamics studies.
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