Glucosepane

7/23/2019 Glucosepane

http://slidepdf.com/reader/full/glucosepane 1/18

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One Ring Glucosepane to bring them all and in the darkness bind them ...

Project idea: fighting the bad guysOne Ring to rule them all, One Ring to find them,



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Why do those guys look so ugly without helmets?Because they hae a

lot of crosslinksbetween !roteinscaused by

"danced #lycationProducts $ "#%s &,

es!ecially in collagen'

"nd collagen is 35%of all !rotein mass in the body



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(s it only about skin?

)o :$



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*ome conse+uences:

"therosclerosis-

idney disease-

%ye diseases $crosslinks are created in cristallin in the eye&

"nd, of course, bad skin'



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/raghici et al. *cience0123

4ow glycation works

Protein glycation:

● non5en6ymatic !rocess● !rotein side chains react with o!en5chain carbohydrates.● glycation !roducts are critically inoled in both healthy and disease



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*ame in short

7 "danced#lycation

%nd5Products

$"#%s&8

!roteins 9ross5linked!roteins


http://slidepdf.com/reader/full/glucosepane 7/18>> 0 >> 1 >> 2 >> 3 >> 4 >>

%am!le of a Bullet Point *lide

Bullet Point 2

Bullet Point 0

*ub Bullet



#lucose!ane the /ark ;ord of

"#%s

92<4=0)>O>

he concentration is 21 to 2111

then any other cross5linking "#%

One for the /ark ;ord on his dark throne(n the ;and of @ordor where the *hadows lie.

9rosslinks A 31 of collagen in !eo!lewith diabetes and A =1 of collagen

in !eo!le older than 31 years



/raghici et al. *cience0123

utorial: 4ow to become a /ark ;ord of "#%sfor dummies /5glucose



*o what to do and who is guilty?

*eeral methods may !reent the formation of glucose!ane in io,

but no method of removing or breakingglucosepane cross-links has been found so far

Possible solutions:

5 The design of drugs thatcan react with the crosslinkswithout breaking any essential

structures. $"labebriumCseffects are not enough inhumans&

5 Finding or engineeringenymes to break the crosslinks.

!here to get enoughglucosepane for testing"



ake itamins? Benfotiamine?

)

)

)

O O

O O4

O

4O

*

P

)40

#ecreases formation of $Gs up to &'%



Pathway of B2

(till scared"!ant to breake)isting cross-links"

)

)

)

O

O

O O4

O

4O

*

P

)40 ●

B2 is similar to Benfotiaminebut not as good

Other ty!es of !reention:

D5/icarbonyl tra!

hia6olium salts

%9@ turnoer



4ow to fight glucose!ane?

#andalfEs "ubrey/e #reyEs adice

9oncise total synthesisof glucose!ane

*cience 2> October 0123:Fol. =31 no. >03< !!. 0GH50G</O(: 21.220>Iscience.aacG>33

*o, now "ubrey can

send a lot of glucose!ane



4ow to detect cross5links breaking

emission " 8 ecitation B



Rings to fight with

%9 )umber: =.3.0.J

%9 )umber: =.3.0.3



%les /irected eolution for rescue*ey steps in the cycle of directed evolution+

@.*. Packer and /.R. ;iu, 0123, )ature

2: original en6yme



Ryan %. 9obb et

al. 0120,

/irected eoluton continues ...



4") KOL

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Glucosepane