Using aza-proline for the assembly of a melanostatin aza-peptide derivative

<p>Selectively targeting cell nucleolus remains a challenge. Here we report the first case that D-peptides form membraneless molecular condensates with RNA for targeting cell nucleolus. A D-peptide derivative, enriched with lysine and hydrophobic residues, self-assembles to form nanoparticles, which enter cells through clathrin dependent endocytosis and mainly accumulate at cell nucleolus. Structural analogue of the D-peptide reveals that particle morphology of the assemblies, which depends on the side chain modification, favors the cellular uptake. Contrasting to those of the D-peptide, the assemblies of the corresponding L-enantiomer largely localize in cell lysosomes. Preliminary mechanism study suggests that the D-peptide nanoparticles interact with RNA to form membraneless condensates in the nucleolus, which further induces DNA damage and results in cell death. This work illustrates a new strategy for rationally designing supramolecular assemblies of D-peptides for targeting subcellular organelles.</p>

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A synthetic peptide derivative that is a cholecystokinin receptor antagonist.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)48227-0 ◽

1987 ◽

Vol 262 (15) ◽

pp. 7226-7231 ◽

Cited By ~ 1

Author(s):

M F Lignon ◽

M C Galas ◽

M Rodriguez ◽

J Laur ◽

A Aumelas ◽

...

Keyword(s):

Receptor Antagonist ◽

Synthetic Peptide ◽

Cholecystokinin Receptor ◽

Peptide Derivative

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Macrophage stimulation with Murabutide, an HIV-suppressive muramyl peptide derivative, selectively activates extracellular signal-regulated kinases 1 and 2, C / EBPβ and STAT1: role of CD14 and Toll-like receptors 2 and 4

European Journal of Immunology ◽

10.1002/1521-4141(200107)31:7<1962::aid-immu1962>3.0.co;2-v ◽

2001 ◽

Vol 31 (7) ◽

pp. 1962-1971 ◽

Cited By ~ 31

Author(s):

Vincent F. Vidal ◽

Nathalie Castéran ◽

Carrie J. Riendeau ◽

Hardy Kornfeld ◽

Edith C. A. Darcissac ◽

...

Keyword(s):

Toll Like Receptors ◽

Muramyl Peptide ◽

Extracellular Signal ◽

Macrophage Stimulation ◽

Peptide Derivative

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557 A peptide derivative with known anti-wrinkle properties was identified as potent dipeptiylpeptidase-4 inhibitor

Journal of Investigative Dermatology ◽

10.1016/j.jid.2016.02.595 ◽

2016 ◽

Vol 136 (5) ◽

pp. S98

Author(s):

D. Imfeld ◽

E. Jackson ◽

E. Wandeler ◽

P. Lais ◽

R. Campiche

Keyword(s):

Peptide Derivative

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Molecular design to mimic the copper(II) transport site of human albumin: studies of equilibria between copper(II) and glycylglycyl-L-histidine-N-methyl amide and comparison with human albumin

Canadian Journal of Chemistry ◽

10.1139/v76-184 ◽

1976 ◽

Vol 54 (8) ◽

pp. 1300-1308 ◽

Cited By ~ 33

Author(s):

Theo P. A. Kruck ◽

Show-Jy Lau ◽

Bibudhendra Sarkar

Keyword(s):

Ternary System ◽

Equilibrium Dialysis ◽

Human Albumin ◽

Binary Complex ◽

Mixed Complex ◽

Free Peptide ◽

System L ◽

Peptide Derivative ◽

Carboxyl Terminal ◽

Transport Site

In continuing the investigation of designing the specific Cu(II)-transport site of human serum albumin, the peptide derivative glycylglycyl-L-histidine-N-methyl amide was designed to approximate more closely to the native protein. This peptide derivative was synthesized in good yield. The equilibria involved in the binary system, Cu(II)–glycylglycyl-L-histidine-N-methyl amide, have been studied, as well as those in the ternary system, L-histidine–Cu(II)–glycylglycyl-L-histidine-N-methyl amide. This peptide derivative was found to bind Cu(II) exclusively as a 1:1 complex in the pH range 4 to 11, having the same ligand atoms as those for the carboxyl-terminal free peptide and human albumin. However, it was found that glycylglycyl-L-histidine-N-methyl amide bound Cu(II) more strongly than did glycylglycyl-L-histidine, the stability constants being log β1–21 = −0.479 and −1.99 respectively. In the ternary system, only 10% of the mixed complex was detected at pH 7, in comparison to 80% found in the case of the carboxyl-terminal free peptide. This finding agrees well with the increased stability of this peptide binary complex. These observations are also consistent with the results obtained from the equilibrium dialysis experiments. The Cu(II) – peptide amide complex has a dissociation constant of 2.07 × 10−17, indicating a higher binding strength of this peptide derivative for Cu(II) over the native albumin by a factor of 3.

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A Peptide Derivative Developed with a Focus on Hair-surface Structure and Its Application to Silicone-Free Conditioner

Journal of Society of Cosmetic Chemists of Japan ◽

10.5107/sccj.47.301 ◽

2013 ◽

Vol 47 (4) ◽

pp. 301-307

Author(s):

Sayaka Nakamura ◽

Eriko Kobayashi ◽

Natsuko Hayashi ◽

Noriyuki Murakoshi ◽

Ayako Koyanagi ◽

...

Keyword(s):

Surface Structure ◽

Peptide Derivative ◽

Hair Surface

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New Unusual Alkaloids from the Ascidian Eudistoma vannamei

Natural Product Communications ◽

10.1177/1934578x1400901212 ◽

2014 ◽

Vol 9 (12) ◽

pp. 1934578X1400901 ◽

Cited By ~ 1

Author(s):

Antônia Torres Ávila Pimenta ◽

Paula Christine Jimenez ◽

Letícia Veras Costa-Lotufo ◽

Raimundo Braz-Filho ◽

Mary Anne Sousa Lima

Keyword(s):

Mass Spectrometry ◽

Meoh Extract ◽

Peptide Derivative ◽

New Compounds ◽

Related Compounds

The MeOH extract of the ascidian Eudistoma vannamei was found to contain three novel compounds, the adenine alkaloid derivatives 9-[ N-(leucyl)-isoleucyl]-adenine (1) and 8-hydroxy-8-isopentyl-7,8-dihydroadenine (2), and the phenylalanine peptide derivative N-[ N-(leucyl)-isoleucyl]phenethylamine (3). Other previously related compounds isolated from this extract include thymidine, 2′-deoxyuridine and phenylalanine. The structures of the new compounds were elucidated through the use of NMR and mass spectrometry.

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CD8β Increases CD8 Coreceptor Function and Participation in TCR–Ligand Binding

Journal of Experimental Medicine ◽

10.1084/jem.184.6.2439 ◽

1996 ◽

Vol 184 (6) ◽

pp. 2439-2444 ◽

Cited By ~ 65

Author(s):

Valery Renard ◽

Pedro Romero ◽

Eric Vivier ◽

Bernard Malissen ◽

Immanuel F. Luescher

Keyword(s):

T Cell ◽

Ligand Binding ◽

Cell Function ◽

Cytotoxic T Lymphocyte ◽

Photoaffinity Labeling ◽

Interleukin 2 ◽

Cell Receptor ◽

Β Cells ◽

Cd8 Cells ◽

Peptide Derivative

To study the role of CD8β in T cell function, we derived a CD8α/β− (CD8−/−) T cell hybridoma of the H-2Kd–restricted N9 cytotoxic T lymphocyte clone specific for a photoreactive derivative of the Plasmodium berghei circumsporozoite peptide PbCS 252-260. This hybridoma was transfected either with CD8α alone or together with CD8β. All three hybridomas released interleukin 2 upon incubation with L cells expressing Kd–peptide derivative complexes, though CD8α/β cells did so more efficiently than CD8α/α and especially CD8−/− cells. More strikingly, only CD8α/β cells were able to recognize a weak agonist peptide derivative variant. This recognition was abolished by Fab′ fragments of the anti-Kd α3 monoclonal antibody SF11.1.1 or substitution of Kd D-227 with K, both conditions known to impair CD8 coreceptor function. T cell receptor (TCR) photoaffinity labeling indicated that TCR–ligand binding on CD8α/β cells was ∼5- and 20-fold more avid than on CD8α/a and CD8−/− cells, respectively. SF1-1.1.1 Fab′ or Kd mutation D227K reduced the TCR photoaffinity labeling on CD8α/β cells to approximately the same low levels observed on CD8−/− cells. These results indicate that CD8α/β is a more efficient coreceptor than CD8α/α, because it more avidly strengthens TCR–ligand binding.

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CD8β Endows CD8 with Efficient Coreceptor Function by Coupling T Cell Receptor/CD3 to Raft-associated CD8/p56lck Complexes

Journal of Experimental Medicine ◽

10.1084/jem.194.10.1485 ◽

2001 ◽

Vol 194 (10) ◽

pp. 1485-1495 ◽

Cited By ~ 158

Author(s):

Alexandre Arcaro ◽

Claude Grégoire ◽

Talitha R. Bakker ◽

Lucia Baldi ◽

Martin Jordan ◽

...

Keyword(s):

T Cell ◽

Ligand Binding ◽

T Cell Receptor ◽

T Cell Activation ◽

Cd8 T Cells ◽

Cell Activation ◽

Cell Receptor ◽

High Affinity ◽

Histocompatibility Complex ◽

Peptide Derivative

The extraordinary sensitivity of CD8+ T cells to recognize antigen impinges to a large extent on the coreceptor CD8. While several studies have shown that the CD8β chain endows CD8 with efficient coreceptor function, the molecular basis for this is enigmatic. Here we report that cell-associated CD8αβ, but not CD8αα or soluble CD8αβ, substantially increases the avidity of T cell receptor (TCR)-ligand binding. To elucidate how the cytoplasmic and transmembrane portions of CD8β endow CD8 with efficient coreceptor function, we examined T1.4 T cell hybridomas transfected with various CD8β constructs. T1.4 hybridomas recognize a photoreactive Plasmodium berghei circumsporozoite (PbCS) peptide derivative (PbCS (4-azidobezoic acid [ABA])) in the context of H-2Kd, and permit assessment of TCR-ligand binding by TCR photoaffinity labeling. We find that the cytoplasmic portion of CD8β, mainly due to its palmitoylation, mediates partitioning of CD8 in lipid rafts, where it efficiently associates with p56lck. In addition, the cytoplasmic portion of CD8β mediates constitutive association of CD8 with TCR/CD3. The resulting TCR-CD8 adducts exhibit high affinity for major histocompatibility complex (MHC)-peptide. Importantly, because CD8αβ partitions in rafts, its interaction with TCR/CD3 promotes raft association of TCR/CD3. Engagement of these TCR/CD3-CD8/lck adducts by multimeric MHC-peptide induces activation of p56lck in rafts, which in turn phosphorylates CD3 and initiates T cell activation.

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