Aminocyclitol‐Substituted Phytoceramides and their Effects on iNKT Cell Stimulation

Harrak, Youssef; Barra, Carolina; Bedia, Carmen; Delgado, Antonio; Castaño, A. Raúl; Llebaría, Amadeu

doi:10.1002/cmdc.200900193

Cited by 21 publications

(29 citation statements)

References 44 publications

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“…On the other hands, Llebaria and his co-workers reported that an aminocyclitol analogue (39, Fig. 15) induced a moderate Th2-biased cytokine production and strong proliferation activity (99). Interestingly, both O-and N-inositoltype analogues of 1 (40) showed no bioactivities (97,99).…”

Section: E Modifi Cation Of the Sugar Part Of Krn7000mentioning

confidence: 97%

“…15) induced a moderate Th2-biased cytokine production and strong proliferation activity (99). Interestingly, both O-and N-inositoltype analogues of 1 (40) showed no bioactivities (97,99). C e l u n d o l o a n d h i s c o -w o r k e r s r e p o r t e d t h a t nonglycosidic analogues of 1, L-arabitol analogue (41) and L-threitol one (42), also induced cytokine productions (100).…”

Section: E Modifi Cation Of the Sugar Part Of Krn7000mentioning

confidence: 99%

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Fifteen Years since the Development of KRN7000 – Structure-Activity Relationship Studies on Novel Glycosphingolipids Which Stimulate Natural Killer T Cells

Tashiro¹,

Mori

2010

TIGG

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Invariant natural killer (NK) T cells bridge innate and acquired immunity and play an important role in both protective and regulatory responses. NKT cell responses are induced by recognition of a complex of glycolipid antigens with CD1d, an antigen presenting protein of the immune system, with its invariant T cell receptors. KRN7000, an α-galactosyl ceramide developed by KIRIN Brewery Co. in 1995, stimulates NKT cells strongly to induce the production of a large amount of cytokines, and is used as a standard reagent for a positive control of NKT cell studies. At the beginning, KRN7000 was developed as an anticancer drug candidate. However, it induces both helper T (Th)1-type cytokines, which induce immunostimulatory activity, and Th2-type ones, which induce immunosuppressive activities, in large quantities at the same time. Its therapeutical use, therefore, is limited. Fifteen years has passed since the discovery of KRN7000, and a number of analogues of KRN7000 have been developed worldwide to solve the above problem. Many researchers are also trying to understand how NKT cells recognize the structure of glycolipids and induce cytokines. In this minireview, we discuss the structure-activity relationship studies on novel glycolipids which stimulate NKT cells efficiently.

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Section: E Modifi Cation Of the Sugar Part Of Krn7000mentioning

confidence: 97%

Section: E Modifi Cation Of the Sugar Part Of Krn7000mentioning

confidence: 99%

Fifteen Years since the Development of KRN7000 – Structure-Activity Relationship Studies on Novel Glycosphingolipids Which Stimulate Natural Killer T Cells

Tashiro¹,

Mori

2010

TIGG

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“…76) Castaño, Llebaria, and co-workers reported that an aminocyclitol analog (HS44, 47) induced weak cytokine production and strong proliferation activity. 118) Neither O-nor N-inositol-type analog of 1 showed bioactivity. 76,118,119) Introducing a functional group, such as a hydroxy or a sulfonyl group (48 and 49 respectively) at the 6 0 -position of the inositol group might diminish immunostimulative activities.…”

Section: )mentioning

confidence: 98%

“…118) Neither O-nor N-inositol-type analog of 1 showed bioactivity. 76,118,119) Introducing a functional group, such as a hydroxy or a sulfonyl group (48 and 49 respectively) at the 6 0 -position of the inositol group might diminish immunostimulative activities. 76,[118][119][120] As non-glycopyranosyl analogs of 1, Celundolo and co-workers reported that an L-arabitol analog (50) and an L-threitol one (51) also induced cytokine production.…”

Section: )mentioning

confidence: 98%

“…76,118,119) Introducing a functional group, such as a hydroxy or a sulfonyl group (48 and 49 respectively) at the 6 0 -position of the inositol group might diminish immunostimulative activities. 76,[118][119][120] As non-glycopyranosyl analogs of 1, Celundolo and co-workers reported that an L-arabitol analog (50) and an L-threitol one (51) also induced cytokine production. [119][120][121] Especially, they found that threitol ceramide 51 was an effective adjuvant for priming both T-and B-cell responses.…”

Section: )mentioning

confidence: 99%

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Structure-Activity Relationship Studies of Novel Glycosphingolipids That Stimulate Natural Killer T-Cells

Tashiro

2012

Bioscience, Biotechnology, and Biochemistry

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New Paradigm in NKT Cell Antigens: MCS‐0208 (2‐(Hydroxymethyl)phenylthio‐phytoceramide) – an Aryl‐Phytoceramide Compound with a Single Hydroxyl Group Stimulates NKT Cells

et al. 2021

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Natural Killer T (NKT) cells play an important role in the immune response and can be activated by glycolipids presented by CD1d protein. We present MCS‐0208, an unprecedented arylthioether‐phytoceramide able to induce potent invariant NKT (iNKT) cell activation, notably when tested in human iNKT cells. This arylsphingolipid analog has a simple phenyl group containing a single hydroxyl substituent as a surrogate of the sugar ring. The phenylthioether structure contrasts with α‐galactosylceramide (1), the prototypical glycolipid used to induce iNKT cell stimulation, where the galactose 2’‐OH and 3’‐OH substituents are accepted as the minimal footprint and considered critical for NKT T cell receptor (TCR) recognition. A computational study supports the recognition of aromatic compound by the CD1d and TCR proteins as radically new structures for NKT cell stimulation.

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Aminocyclitol‐Substituted Phytoceramides and their Effects on iNKT Cell Stimulation

Cited by 21 publications

References 44 publications

Fifteen Years since the Development of KRN7000 – Structure-Activity Relationship Studies on Novel Glycosphingolipids Which Stimulate Natural Killer T Cells

Fifteen Years since the Development of KRN7000 – Structure-Activity Relationship Studies on Novel Glycosphingolipids Which Stimulate Natural Killer T Cells

Structure-Activity Relationship Studies of Novel Glycosphingolipids That Stimulate Natural Killer T-Cells

New Paradigm in NKT Cell Antigens: MCS‐0208 (2‐(Hydroxymethyl)phenylthio‐phytoceramide) – an Aryl‐Phytoceramide Compound with a Single Hydroxyl Group Stimulates NKT Cells

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