PMID- 37376220
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230701
IS  - 1999-4923 (Print)
IS  - 1999-4923 (Electronic)
IS  - 1999-4923 (Linking)
VI  - 15
IP  - 6
DP  - 2023 Jun 20
TI  - Dipropyleneglycol Dimethylether, New Green Solvent for Solid-Phase Peptide 
      Synthesis: Further Challenges to Improve Sustainability in the Development of 
      Therapeutic Peptides.
LID - 10.3390/pharmaceutics15061773 [doi]
LID - 1773
AB  - In recent years, peptides have gained more success as therapeutic compounds. 
      Nowadays, the preferred method to obtain peptides is solid-phase peptide 
      synthesis (SPPS), which does not respect the principles of green chemistry due to 
      the large number of toxic reagents and solvents used. The aim of this work was to 
      research and study an environmentally sustainable solvent able to replace 
      dimethylformamide (DMF) in fluorenyl methoxycarbonyl (Fmoc) solid-phase peptide 
      synthesis. Herein, we report the use of dipropyleneglycol dimethylether (DMM), a 
      well-known green solvent with low human toxicity following oral, inhalant, and 
      dermal exposure and that is easily biodegradable. Some tests were needed to 
      evaluate its applicability to all the steps of SPPS, such as amino acid 
      solubility, resin swelling, deprotection kinetics, and coupling tests. Once the 
      best green protocol was established, it was applied to the synthesis of different 
      length peptides to study some of the fundamental parameters of green chemistry, 
      such as PMI (process mass intensity) and the recycling of solvent. It was 
      revealed that DMM is a valuable alternative to DMF in all steps of solid-phase 
      peptide synthesis.
FAU - Vivenzio, Giovanni
AU  - Vivenzio G
AD  - Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 
      Fisciano, 84084 Salerno, Italy.
FAU - Scala, Maria Carmina
AU  - Scala MC
AD  - Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 
      Fisciano, 84084 Salerno, Italy.
FAU - Marino, Pasquale
AU  - Marino P
AUID- ORCID: 0009-0000-1796-8024
AD  - Department of Sciences, University of Basilicata, Via dell'Ateneo Lucano 10, 
      85100 Potenza, Italy.
FAU - Manfra, Michele
AU  - Manfra M
AUID- ORCID: 0000-0002-3320-972X
AD  - Department of Sciences, University of Basilicata, Via dell'Ateneo Lucano 10, 
      85100 Potenza, Italy.
FAU - Campiglia, Pietro
AU  - Campiglia P
AUID- ORCID: 0000-0002-1069-2181
AD  - Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 
      Fisciano, 84084 Salerno, Italy.
FAU - Sala, Marina
AU  - Sala M
AUID- ORCID: 0000-0003-2739-7215
AD  - Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 
      Fisciano, 84084 Salerno, Italy.
LA  - eng
PT  - Journal Article
DEP - 20230620
PL  - Switzerland
TA  - Pharmaceutics
JT  - Pharmaceutics
JID - 101534003
PMC - PMC10304503
OTO - NOTNLM
OT  - dipropyleneglycol dimethylether
OT  - green chemistry
OT  - peptides
OT  - recycling
OT  - solid-phase peptide synthesis
COIS- The authors declare no conflict of interest.
EDAT- 2023/06/28 06:42
MHDA- 2023/06/28 06:43
PMCR- 2023/06/20
CRDT- 2023/06/28 01:37
PHST- 2023/05/30 00:00 [received]
PHST- 2023/06/15 00:00 [revised]
PHST- 2023/06/16 00:00 [accepted]
PHST- 2023/06/28 06:43 [medline]
PHST- 2023/06/28 06:42 [pubmed]
PHST- 2023/06/28 01:37 [entrez]
PHST- 2023/06/20 00:00 [pmc-release]
AID - pharmaceutics15061773 [pii]
AID - pharmaceutics-15-01773 [pii]
AID - 10.3390/pharmaceutics15061773 [doi]
PST - epublish
SO  - Pharmaceutics. 2023 Jun 20;15(6):1773. doi: 10.3390/pharmaceutics15061773.