PMID- 36385929
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240211
IS  - 1948-5875 (Print)
IS  - 1948-5875 (Electronic)
IS  - 1948-5875 (Linking)
VI  - 13
IP  - 11
DP  - 2022 Nov 10
TI  - Discovery of kappa Opioid Receptor (KOR)-Selective d-Tetrapeptides with Improved In 
      Vivo Antinociceptive Effect after Peripheral Administration.
PG  - 1707-1714
LID - 10.1021/acsmedchemlett.2c00237 [doi]
AB  - Peripherally active tetrapeptides as selective kappa opioid receptor (KOR) agonists 
      have been prepared in good overall yields and high purity following solid-phase 
      peptide synthesis via Fmoc protection strategy. Structural modifications at the 
      first and second position of the lead compound FF(d-Nle)R-NH(2) (FE200041) were 
      contemplated with aromatic side chains containing d-amino acids, such as 
      (d)-pF-Phe, (d)-mF-Phe, (d)-oF-Phe, which led to highly selective and efficacious 
      KOR agonists endowed with strong antinociceptive activity in vivo following 
      intravenous (i.v.) and subcutaneous (s.c.) administration in the tail flick and 
      formalin tests. These results suggest potential clinical applications in the 
      treatment of neuropathic and inflammatory pain.
CI  - (c) 2022 American Chemical Society.
FAU - Stefanucci, Azzurra
AU  - Stefanucci A
AUID- ORCID: 0000-0001-7525-2913
AD  - Dipartimento di Farmacia, Universita di Chieti-Pescara "G. d'Annunzio", Via dei 
      Vestini 31, 66100 Chieti, Italy.
FAU - Della Valle, Alice
AU  - Della Valle A
AD  - Dipartimento di Farmacia, Universita di Chieti-Pescara "G. d'Annunzio", Via dei 
      Vestini 31, 66100 Chieti, Italy.
FAU - Scioli, Giuseppe
AU  - Scioli G
AD  - Dipartimento di Farmacia, Universita di Chieti-Pescara "G. d'Annunzio", Via dei 
      Vestini 31, 66100 Chieti, Italy.
FAU - Marinaccio, Lorenza
AU  - Marinaccio L
AD  - Dipartimento di Farmacia, Universita di Chieti-Pescara "G. d'Annunzio", Via dei 
      Vestini 31, 66100 Chieti, Italy.
FAU - Pieretti, Stefano
AU  - Pieretti S
AUID- ORCID: 0000-0001-5926-6194
AD  - Istituto Superiore di Sanita, Centro Nazionale Ricerca e Valutazione Preclinica e 
      Clinica dei farmaci, Viale Regina Elena 299, 00161 Rome, Italy.
FAU - Minosi, Paola
AU  - Minosi P
AD  - Istituto Superiore di Sanita, Centro Nazionale Ricerca e Valutazione Preclinica e 
      Clinica dei farmaci, Viale Regina Elena 299, 00161 Rome, Italy.
FAU - Szucs, Edina
AU  - Szucs E
AD  - Institute of Biochemistry, Biological Research Centre, 6726 Szeged, Hungary.
FAU - Benyhe, Sandor
AU  - Benyhe S
AD  - Institute of Biochemistry, Biological Research Centre, 6726 Szeged, Hungary.
FAU - Masci, Domiziana
AU  - Masci D
AD  - Department of Basic Biotechnological Sciences, Intensivological and Perioperative 
      Clinics, Catholic University of Sacred Heart, Largo Francesco Vito 1, 00168 Rome, 
      Italy.
FAU - Tanguturi, Parthasaradhireddy
AU  - Tanguturi P
AD  - Department of Pharmacology, College of Medicine, University of Arizona, Tucson, 
      Arizona 85724, United States.
FAU - Chou, Kerry
AU  - Chou K
AD  - Department of Pharmacology, College of Medicine, University of Arizona, Tucson, 
      Arizona 85724, United States.
FAU - Barlow, Deborah
AU  - Barlow D
AD  - Department of Biomedical Sciences, College of Osteopathic Medicine, University of 
      New England, Biddeford, Maine 04005, United States.
FAU - Houseknecht, Karen
AU  - Houseknecht K
AD  - Department of Biomedical Sciences, College of Osteopathic Medicine, University of 
      New England, Biddeford, Maine 04005, United States.
FAU - Streicher, John M
AU  - Streicher JM
AD  - Department of Pharmacology, College of Medicine, University of Arizona, Tucson, 
      Arizona 85724, United States.
FAU - Mollica, Adriano
AU  - Mollica A
AUID- ORCID: 0000-0002-7242-4860
AD  - Dipartimento di Farmacia, Universita di Chieti-Pescara "G. d'Annunzio", Via dei 
      Vestini 31, 66100 Chieti, Italy.
LA  - eng
GR  - R01 DA052340/DA/NIDA NIH HHS/United States
PT  - Journal Article
DEP - 20221017
PL  - United States
TA  - ACS Med Chem Lett
JT  - ACS medicinal chemistry letters
JID - 101521073
PMC - PMC9661715
COIS- The authors declare no competing financial interest.
EDAT- 2022/11/18 06:00
MHDA- 2022/11/18 06:01
PMCR- 2023/11/10
CRDT- 2022/11/17 11:35
PHST- 2022/05/21 00:00 [received]
PHST- 2022/10/13 00:00 [accepted]
PHST- 2022/11/17 11:35 [entrez]
PHST- 2022/11/18 06:00 [pubmed]
PHST- 2022/11/18 06:01 [medline]
PHST- 2023/11/10 00:00 [pmc-release]
AID - 10.1021/acsmedchemlett.2c00237 [doi]
PST - epublish
SO  - ACS Med Chem Lett. 2022 Oct 17;13(11):1707-1714. doi: 
      10.1021/acsmedchemlett.2c00237. eCollection 2022 Nov 10.