Influence of Aza-Glycine Substitution on the Internalization of Penetratin

被引:1
|
作者
Tarchoun, Karima [1 ,2 ]
Soltesz, Dora [1 ,2 ]
Farkas, Viktor [3 ]
Lee, Ho-Jin [4 ,5 ]
Szabo, Ildiko [6 ]
Banoczi, Zoltan [1 ]
机构
[1] Eotvos Lorand Univ, Inst Chem, Fac Sci, Pazmany Peter Setany 1-A, H-1117 Budapest, Hungary
[2] ELTE Eotvos Lorond Univ, Inst Chem, Hevesy Gyorgy PhD Sch Chem, Pazmany Peter Setany 1-A, H-1117 Budapest, Hungary
[3] Eotvos Lorand Univ, Inst Chem, HUN REN ELTE Prot Modeling Res Grp, Pazmany Peter Setany 1-A, H-1117 Budapest, Hungary
[4] Southwest Tennessee Community Coll, Dept Nat Sci, Memphis, TN 38015 USA
[5] LeMoyne Own Coll, Div Nat & Math Sci, Memphis, TN 38126 USA
[6] HUN REN ELTE Res Grp Peptide Chem, H-1117 Budapest, Hungary
基金
新加坡国家研究基金会;
关键词
cell-penetrating peptides; penetratin; aza-amino acid; aza-peptide; flow cytometry; TROJAN PEPTIDE PENETRATIN; ARGININE-RICH PEPTIDES; CELLULAR UPTAKE; AZAPEPTIDES; AZAPROLINE; RESIDUE; ANALOGS; MACROPINOCYTOSIS; TRANSLOCATION; ENDOCYTOSIS;
D O I
10.3390/pharmaceutics16040477
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The cell-penetrating peptide (CPP) penetratin has gained much attention over many years due to its potential role as a transporter for a broad range of cargo into cells. The modification of penetratin has been extensively investigated too. Aza-peptides are peptide analogs in which one or more of the amino residues are replaced by a semicarbazide. This substitution results in conformational restrictions and modifications in hydrogen bonding properties, which affect the structure and may lead to enhanced activity and selectivity of the modified peptide. In this work, the Trp residues of penetratin were substituted by aza-glycine or glycine residues to examine the effect of these modifications on the cellular uptake and the internalization mechanism. The substitution of Trp48 or Trp48,56 dramatically reduced the internalization, showing the importance of Trp48 in cellular uptake. Interestingly, while aza-glycine in the position of Trp56 increased the cellular uptake, Gly reduced it. The two Trp-modified derivatives showed altered internalization pathways, too. Based on our knowledge, this is the first study about the effect of aza-amino acid substitution on the cell entry of CPPs. Our results suggest that aza-amino acid insertion is a useful modification to change the internalization of a CPP.
引用
收藏
页数:13
相关论文
共 50 条
  • [21] Glycine binding primes NMDA receptor internalization
    Yi Nong
    Yue-Qiao Huang
    William Ju
    Lorraine V. Kalia
    Gholamreza Ahmadian
    Yu Tian Wang
    Michael W. Salter
    Nature, 2003, 422 : 302 - 307
  • [22] ORGN 205-Influence of aza substitution on racemization barriers and acidobasic properties of helicenes
    Chocholousova, Jana
    Vacek, Jaroslav
    Misek, Jiri
    Stara, Irena G.
    Stary, Ivo
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2009, 237
  • [23] ELECTROCHEMICAL REDUCTION OF AZA-AROMATICS .5. INFLUENCE OF FLUORINE SUBSTITUTION ON ELECTRON AFFINITIES
    VANDENHAM, DMW
    HARRISON, GFS
    SPAANS, A
    VANDERMEER, D
    RECUEIL DES TRAVAUX CHIMIQUES DES PAYS-BAS-JOURNAL OF THE ROYAL NETHERLANDS CHEMICAL SOCIETY, 1975, 94 (07): : 168 - 173
  • [24] Structural Bases for the Involvement of Phosphatidylinositol-4,5-bisphosphate in the Internalization of the Cell-Penetrating Peptide Penetratin
    Bechtella, Leila
    Chalouhi, Edward
    Rodriguez, Paula Milan
    Cosset, Marine
    Ravault, Delphine
    Illien, Francoise
    Sagan, Sandrine
    Carlier, Ludovic
    Lequin, Olivier
    Fuchs, Patrick F. J.
    Sachon, Emmanuelle
    Walrant, Astrid
    ACS CHEMICAL BIOLOGY, 2022, 17 (06) : 1427 - 1439
  • [25] Monitoring penetratin interactions with lipid membranes and cell internalization using a new hydration-sensitive fluorescent probe
    Zamotaiev, Oleksandr M.
    Postupalenko, Viktoriia Y.
    Shvadchak, Volodymyr V.
    Pivovarenko, Vasyl G.
    Klymchenko, Andrey S.
    Mely, Yves
    ORGANIC & BIOMOLECULAR CHEMISTRY, 2014, 12 (36) : 7036 - 7044
  • [26] Relationships between Membrane Binding, Affinity and Cell Internalization Efficacy of a Cell-Penetrating Peptide: Penetratin as a Case Study
    Alves, Isabel D.
    Bechara, Cherine
    Walrant, Astrid
    Zaltsman, Yefim
    Jiao, Chen-Yu
    Sagan, Sandrine
    PLOS ONE, 2011, 6 (09):
  • [27] EFFECT OF AZA-SUBSTITUTION AND ALKYL SUBSTITUTION ON SOLUBILITY AND THERMODYNAMICS OF PORPHYRIN MOLECULE SOLUTIONS
    BEREZIN, BD
    KHELEVINA, OG
    TROFIMENKO, GM
    ZHURNAL FIZICHESKOI KHIMII, 1991, 65 (08): : 2055 - 2059
  • [28] AZA-SUBSTITUTION VERSUS PHOSPHA-SUBSTITUTION IN CYCLOBUTADIENE - A THEORETICAL EVALUATION OF BONDING PROPERTIES
    SCHOELLER, WW
    BUSCH, T
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION IN ENGLISH, 1993, 32 (04): : 617 - 619
  • [29] INFLUENCE OF BASICITY OF AZA-GROUP UPON DIRECTION OF NUCLEOPHYLIC SUBSTITUTION REACTION IN IMIDAZO[4,5-]QUINOLINES
    KHRISTICH, BI
    KRUCHINI.VA
    POZHARSK.AF
    SIMONOV, AM
    KHIMIYA GETEROTSIKLICHESKIKH SOEDINENII, 1971, (06): : 814 - +
  • [30] Synthesis of π-Conjugated Chiral Aza/Boracyclophanes with a meta and para Substitution
    Zhang, Kai
    Hao, Mengyao
    Jin, Tianyun
    Shi, Yafei
    Tian, Guoqing
    Li, Chenglong
    Ma, Hongwei
    Zhang, Niu
    Li, Quansong
    Chen, Pangkuan
    CHEMISTRY-A EUROPEAN JOURNAL, 2024, 30 (05)