Peptides as Therapeutic Agents: Challenges and Opportunities in the Green Transition Era

Abstract

Peptides are at the cutting edge of contemporary research for new potent, selective, and safe therapeutical agents. Their rise has reshaped the pharmaceutical landscape, providing solutions to challenges that traditional small molecules often cannot address. A wide variety of natural and modified peptides have been obtained and studied, and many others are advancing in clinical trials, covering multiple therapeutic areas. As the demand for peptide-based therapies grows, so does the need for sustainable and environmentally friendly synthesis methods. Traditional peptide synthesis, while effective, often involves environmentally draining processes, generating significant waste and consuming vast resources. The integration of green chemistry offers sustainable alternatives, prioritizing eco-friendly processes, waste reduction, and energy conservation. This review delves into the transformative potential of applying green chemistry principles to peptide synthesis by discussing relevant examples of the application of such approaches to the production of active pharmaceutical ingredients (APIs) with a peptide structure and how these efforts are critical for an effective green transition era in the pharmaceutical field.

Degradation of the α-Carboxyl Terminus 11 Peptide: In Vivo and Ex Vivo Impacts of Time, Temperature, Inhibitors, and Gender in Rat

“…18 The present study found that the addition of a mixture of these inhibitory compounds significantly mitigated αCT11 degradation after 30 min incubation at both 22 and 37 °C and after 60 min incubation at 22 °C (Figure 5), leading to an overall increase of half-life to about 30−50 min at 37 °C, which could significantly accelerate therapeutic efficacy in protein or peptide-based therapies. 63 However, the cocktail of inhibitors used in the present study is unlikely to be used for clinical management because of the likelihood of side effects from some, or all, of the components in such mixtures. For this reason, other strategies must be explored to reach the same goal of increasing the stability and half-life of therapeutic peptides.…”

“…As such, antagonists have the potential to increase the half-life of therapeutic peptides undergoing clinical testing. , In lab research, PTase/PPTase inhibitor cocktails are commonly used together with cell lysis reagents to prevent degradation of extracted proteins for various protein analyses, such as Western blot . The present study found that the addition of a mixture of these inhibitory compounds significantly mitigated αCT11 degradation after 30 min incubation at both 22 and 37 °C and after 60 min incubation at 22 °C (Figure ), leading to an overall increase of half-life to about 30–50 min at 37 °C, which could significantly accelerate therapeutic efficacy in protein or peptide-based therapies …”

“…However, the cocktail of inhibitors used in the present study is unlikely to be used for clinical management because of the likelihood of side effects from some, or all, of the components in such mixtures. For this reason, other strategies must be explored to reach the same goal of increasing the stability and half-life of therapeutic peptides. ,− For example, fusing a peptide to the stable bacterial Rop (repressor of primer) protein or incorporation of two proline residues has been shown to significantly increase resistance to proteinase-induced degradation . Conjugating alpha1 proteinase inhibitor (α1PI) with poly­(ethylene glycol) (PEG) at Cys (232) has also been observed to extend the in vivo half-life of α1PI in the bloodstream .…”

Oromucosal Administration of Oxytocin: The Development of ‘Oxipops’

“…While oromucosal administration using medicated candies is still a relatively novel strategy and has yet to be fully established for other suitable candidate peptide or non-peptide drugs, it may open up future possible avenues for administering either acute or long-term medication to individuals where other routes are less well-tolerated. In recent years for example, there has been a considerable growth in the number of peptide-based therapeutic drugs, with currently > 80 having been approved for use [ 61 ]. Peptide drugs offer several advantages over small molecules, including a heightened target specificity and potency and reduced side effects, although few have been developed for oromucosal administration.…”

“…Peptide drugs offer several advantages over small molecules, including a heightened target specificity and potency and reduced side effects, although few have been developed for oromucosal administration. A full consideration of the current numerous peptide-based drugs, other than oxytocin, is beyond the scope of the current review and has been covered in another publication (see [ 61 ]). As outlined in Figure 1 , the two obvious potential limitations for the oromucosal administration of peptide-based drugs as opposed to small molecules are that high molecular weights may result in poor penetration through the oral mucosae and that they are often metabolized too rapidly.…”