New perspectives in oral peptide delivery

Zizzari, Alessandra; Pliatsika, Dimanthi; Gall, Flavio M.; Fischer, Thomas; Riedl, Rainer

doi:10.1016/j.drudis.2021.01.020

Cited by 72 publications

(43 citation statements)

References 51 publications

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“…Nevertheless, peptide therapeutics continue to be in the focus of current drug discovery and development projects due to their distinct biological activities in academia as well as industry and show increasing success rates. [30] …”

Section: Discussionmentioning

confidence: 99%

Antiprotozoal Structure–Activity Relationships of Synthetic Leucinostatin Derivatives and Elucidation of their Mode of Action

et al. 2021

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Leucinostatin Ai soneo ft he most potent antiprotozoal compounds ever described, but little was knowno n structure-activity relationships (SAR). We used Trypanosoma brucei as ap rotozoal model organism to test synthetically modified derivatives,r esulting in simplified but equally active compounds 2 (ZHAWOC6025) and 4 (ZHAWOC6027), which were subsequently modified in all regions of the molecule to gain an in-depth SAR understanding.T he antiprotozoal SAR matched SAR in phospholipid liposomes, where membrane integrity,l eaking, and dynamics were studied. The mode of action is discussed based on as tructure-activity analysis of derivatives in efficacy,u ltrastructural studies in T. brucei, and artificial membrane models,m imicking membrane stability and membrane potential. The main site of antiprotozoal action of natural and synthetic leucinostatins lies in the destabilization of the inner mitochondrial membrane,a sd emonstrated by ultrastructural analysis,e lectron microscopya nd mitochondrial staining.L ong-time sublethal exposure of T. brucei (200 passages) and siRNAs creening of 12'000 mutants showed no signs of resistance development to the synthetic derivatives.

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Section: Discussionmentioning

confidence: 99%

Antiprotozoal Structure–Activity Relationships of Synthetic Leucinostatin Derivatives and Elucidation of their Mode of Action

et al. 2021

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“…While holding significant progress, peptide therapeutics still suffer from key limitations associated with: stability (API and formulation [ 99 , 186 , 187 , 188 , 189 ] /in vitro and in vivo [ 190 , 191 , 192 , 193 , 194 ] ); susceptibility to proteases [ 190 , 195 , 196 , 197 , 198 , 199 , 200 ] potential immune (IgG) responses [ 120 , 201 , 202 , 203 ] cost at scale [ 204 , 205 , 206 , 207 ] pharmacokinetic bioavailability. [ 208 , 209 , 210 , 211 , 212 ] Notwithstanding, numerous strategies have been explored to overcome these challenges and others, including self‐assembling peptides from our group [ 213 , 214 , 215 , 216 , 217 , 218 , 219 , 220 ] and others. [ 221 , 222 , 223 , 224 , 225 ]…”

Section: Discussionmentioning

confidence: 99%

Peptide‐Based Inhibitors for SARS‐CoV‐2 and SARS‐CoV

Panchal

Kataria

Patel

et al. 2021

Advanced Therapeutics

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The COVID‐19 (coronavirus disease) global pandemic, caused by the spread of the SARS‐CoV‐2 (severe acute respiratory syndrome coronavirus 2) virus, currently has limited treatment options which include vaccines, anti‐virals, and repurposed therapeutics. With their high specificity, tunability, and biocompatibility, small molecules like peptides are positioned to act as key players in combating SARS‐CoV‐2, and can be readily modified to match viral mutation rate. A recent expansion of the understanding of the viral structure and entry mechanisms has led to the proliferation of therapeutic viral entry inhibitors. In this comprehensive review, inhibitors of SARS and SARS‐CoV‐2 are investigated and discussed based on therapeutic design, inhibitory mechanistic approaches, and common targets. Peptide therapeutics are highlighted, which have demonstrated in vitro or in vivo efficacy, discuss advantages of peptide therapeutics, and common strategies in identifying targets for viral inhibition.

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“…Physical and chemical methods could improve the oral bioavailability and stability of the peptides [127]. This includes pH modulation of intestinal enzymes by adding organic acids such as citric acid and enzyme inhibitors, enteric coating using polyacrylic polymers, and nanoparticles [128,129]. Nanoparticle-coated drugs have shown enhanced bioavailability and distribution [130].…”

Section: Oral Bioavailability and Stability Of Peptide Drugsmentioning

confidence: 99%

Bioactive Peptides as Potential Nutraceuticals for Diabetes Therapy: A Comprehensive Review

Antony

Vijayan

2021

IJMS

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Diabetes mellitus is a major public health concern associated with high mortality and reduced life expectancy. The alarming rise in the prevalence of diabetes is linked to several factors including sedentary lifestyle and unhealthy diet. Nutritional intervention and increased physical activity could significantly contribute to bringing this under control. Food-derived bioactive peptides and protein hydrolysates have been associated with a number health benefits. Several peptides with antidiabetic potential have been identified that could decrease blood glucose level, improve insulin uptake and inhibit key enzymes involved in the development and progression of diabetes. Dietary proteins, from a wide range of food, are rich sources of antidiabetic peptides. Thus, there are a number of benefits in studying peptides obtained from food sources to develop nutraceuticals. A deeper understanding of the underlying molecular mechanisms of these peptides will assist in the development of new peptide-based therapeutics. Despite this, a comprehensive analysis of the antidiabetic properties of bioactive peptides derived from various food sources is still lacking. Here, we review the recent literature on food-derived bioactive peptides possessing antidiabetic activity. The focus is on the effectiveness of these peptides as evidenced by in vitro and in vivo studies. Finally, we discuss future prospects of peptide-based drugs for the treatment of diabetes.

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New perspectives in oral peptide delivery

Cited by 72 publications

References 51 publications

Antiprotozoal Structure–Activity Relationships of Synthetic Leucinostatin Derivatives and Elucidation of their Mode of Action

Antiprotozoal Structure–Activity Relationships of Synthetic Leucinostatin Derivatives and Elucidation of their Mode of Action

Peptide‐Based Inhibitors for SARS‐CoV‐2 and SARS‐CoV

Bioactive Peptides as Potential Nutraceuticals for Diabetes Therapy: A Comprehensive Review

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