►
Description
Open project meeting for Open Source Antibiotics Series 1, the Mur Ligases.
Full Project: https://github.com/opensourceantibiotics/murligase
Relevant GitHub Issue: https://github.com/opensourceantibiotics/murligase/issues/71
On the call: Prof Chris Dowson, Dr Adrian Lloyd, Laura Diaz Saez (University of Warwick), Dr Edwin Tse, Yuhang Wang, Kato Leonard (UCL), Lizbe Koekemoer (Uni Oxford/Diamond), Dr Lori Ferrins, Dr Joe Eyermann (Northeastern University), Dr Jan Jensen (University of Copenhagen), Dr Chris Swain (Cambridge MedChem Consulting), Dr Jan Abendroth, Dr Bart Staker (SSGCID).
A
So
the
dose
response
data
has
been
posted
to
get
habits
on
the
end
of
the
february
meetings.
I
can
link
to
this
meeting
if
I
want-
and
I
think
I
just
need
to
confirm
with
dana
where
she
wants
it
on
the
wiki,
because
I
suppose
it
needs
to
be
in
both
places,
but
it's
all
finished
and
it
is
posted
to
github.
C
Yes,
so
ed
is
on
vacation,
but
we've
been
starting
to
work
on
our
new
fragments,
but
I
think
it's
better
to
give
a
final
update
when
he's
back
and
when
we've
synthesized
them.
But
you
can
click
on
the
link
and
see
which
fragments
we
mean.
These
are
based
on
the
sexual
inhibitors.
That
back
had
the
dose
response
curves
on
and
there
was
one
that
had
the
better
ic50.
I
guess
so
we'll
do
an
update
until
that
next
next
meeting
or
when
we've
had
more
synthesis
done.
A
D
B
C
E
B
D
B
D
B
B
B
F
B
G
G
It
should
be
quick,
but
the
whole
process
was
a
bit
messy
during
this
reaction,
because
90
minutes
was
clearly
a
bit
a
bit
of
too
much.
So
there
are
peaks,
there's
a
one
peak
with
the
rights,
so
there
were,
there
are
multiple
products
being
generated,
so
I
just
I'm
still
working
on
that
about
the
second
section
so
and
about
the
third
section,
the
synthetic
roots
for
young's
predictions
as
we
have
already
discussed
under
it.
B
B
B
B
G
B
G
About
the
ate
their
compounds,
I
think
previously
was
so
the
compound
was,
we
said:
osa
codes,
zero,
zero,
one,
zero,
four
four,
and
it's
also
on
the
on
the
agenda.
It's
also
on
the
gender
part
compound
w,
so
that
compound
was
sent
to
was
sent
to
previous
was
processed
by
peter
and
now
I
think
young's
taking
care
of
it
about
the
crystallography
data
and
yeah.
I
guess
we
only
oh!
I
think
I
guess
we
need
the
final
data
from
young,
maybe
about
to
overlay
it.
G
We
with
azir
5.95
in
pdb
6x9,
and
is
it
a074
in
pdb69f,
I
think
yeah.
So
that's
the
that's
the
product
we
made
from
young
in
the
u.s.
I
think
okay
yeah
and
about
the
second
one
to
ship,
a
z5595
to
ssgci
they
yeah.
I've
already
got
the
very
pure
compounds
and
they
just
it's
a
time
thing.
Matt
wants
me
to
send
other
chemicals
at
the
same
time
to
save
some
shipments
fees,
so
yeah
we'll
probably
delay
that.
B
J
J
Well,
I
mean
for
other
people
with
input,
but
I
I
I've
done
my
part.
Okay,
I'm
concerned.
Okay,
I
mean
we
did.
I
mean
I
guess
I
can't
remember
I
was
in
that
section.
I
mean
we
talked
about
more,
like
truncation
truncated
versions.
I
think
the
other.
Maybe
that's
a
later
discussion
item
or
whatever.
Maybe
I
can't
remember
where
that
falls
in
the
in
the
long
list
about
truncated
versions.
J
F
B
B
B
Cool
I'll
I'll
zip
down
to
six,
then
another
potential
start
point
so
lori
suggested
applying
to
the
merck,
open,
global
health
library.
I
think
this
is
in
lieu
of
us
not
really
having
any
success
with
the
european
lead
factory.
I've
had
a
a
look
at
that,
I'm
actually
halfway
through
drafting
an
initial
exploratory
email
to
them
on
behalf
of
the
whole
group,
but
they
are
prepared
to
give
access
to
compounds
free
ipfree.
B
So
we'll
we'll
open
a
conversation
and
see
what
what
comes
from
that.
But
as
with
that
and
with
the
other
compounds,
I
think
we're
we're
quite
quickly
getting
to
the
point
that
to
maintain
the
bandwidth,
we're
going
to
need
some
more
funding
for
people
to
be
able
to
keep
things.
Turning
over.
So
that's
that'll
be
a
key
key
component
right,
I'm
going
to
no
adrian's
disappeared,
so
I
can't
show
them
and
him
talk
to
them.
K
J
So
so
yeah,
I
guess
I
would
just
chime
in
again.
I
think
we
we've
talked
about
you
know
the
crystal
you
know,
crystallography
has
been
at
least
in
terms
of
getting
with
these
fragments
has
been
a
challenge.
We
we,
you
know
it's
getting
the
right
system
right
in
place
for
that,
and
so
we
did
have
this
disc.
I
mean
I
brought
up
this
idea
of
having
some
truncated
version.
I
guess
the
other
thing,
so
you
guys
know.
J
I
know
in
some
of
the
other
emails
that
you've
actually
made
some
uma
for
the
for
the
biochemical
assays
and
I'm
just
wondering
if
it's
worth
trying
some
of
these
crystallog
crystal
systems
with
uma
bound
to
see
if
that
helps
in
basically
stabilizing
the
system
for
for
with
fragments
yeah.
So
that's
that's
just
I
guess
that's
one
thing
I
would
ask.
Maybe
that
is
possible
to
try
if
you
actually
now
have
uma
in
the
lab
that
could
be
used
for
some
crystal
trials.
That
would
be,
at
least
in
theory.
H
D
D
B
D
J
J
J
M
M
B
B
B
H
Right
good
afternoon,
everyone
sorry
about
the
issue
about
my
video
camera,
so
we're
just
going
to
give
you
an
update
with
regard
to
some
of
the
entomology
that
we've
been
doing
here
with
d
and
the
e
and
I'll
start
with
actually
some
becker's
data.
So
this
is
her
screening
data
with
streptococcus
and
galacti.
H
We
did
that
we
just
made
sure
that
of
the
concentrations
we
needed
to
use
and
we
did
that
by
determining
the
kinetic
constants
of
d
and
e
with
respect
to
atp
and
with
respect
to
murder.
On
the
left-hand
side,
the
km
is
of
the
order
of
70
micromolar
and
with
mer-e
it's
approaching
60
micromolar.
So
what
we
elected
to
do
was
to
drop
the
atp
concentration
in
the
screening
assays
to
20
micromolar,
again,
one-third
of
km
so
we'll
be
working
at
an
equivalent
sensitivity
to
that
that
becca
was
using
with
the
allogalacti
enzyme.
H
H
The
sea
green
color
is
played
as
the
results
from
compounds
in
plane,
ao1
the
purple
from
those
in
place.
O2
the
dmso
vehicle
is,
on
the
left
hand,
side
in
the
with
the
brown
bar
at
100
and
the
positive
control,
which
is
a
millimolar
80
pcp,
which
is
an
atp
analog,
is
on
the
far
right
in
scarlet,
and
essentially,
we
found
three
compounds
in
the
murder
screen
that
fell
with
to
around
about
70
percent,
inhibition,
that
is
to
say,
30
remaining
activity
and
with
murphy.
H
H
So
moving
on
from
this,
because
it's
a
different
assay,
it's
a
fluorescent
acid
compared
to
a
spectrophotometric
assay.
There
are
compounds
in
the
one
technique
that
do
not
that
do
not
actually
have
properties
compatible
with
the
second
one,
and
one
of
these
compounds
is
j06.
In
j06
we
re-assayed
using
the
spectrophotometric
assay
that
becca
had
generated,
but
with
atp,
and
it
turns
out
that
it
is
a
good
inhibitor
of
pseudomonas,
originals
and
murphy
at
one
millimolar,
and
we
have
to
characterize
that
further.
H
So
we
have
a
number
of
things.
We
have
to
confirm,
we
have
the
other
ic50s
of
the
other
compounds
to
do.
We
need
to
do
a
bit
more
mode
of
action.
Work
to
prove
whether
or
not
lo6,
for
example,
actually
does
target
the
atp
binding
site.
So
there'll
be
a
lot
of
competition
essays
to
do-
and
that's
that's
where
we
are
at
the
moment
at
the
moment.
F
B
D
B
J
I
don't
know
whatever
starting
point
and
then
some
number
I
would
rather
see
because
I
think
one
of
the
issues
we
have
going
forward
is
going
to
be.
You
know
how
things
get
resourced
and
where
they
go
into
grants
and
so
on.
So
I
I
would
my
personal
bias
would
be
that
we
would
just
identify
using
some
initial
set
of
characters
that
has
where
the
the
source
of
the
compounds
and
then
some
number.
J
J
J
Yeah
yeah,
like
I
think
I
think
at
the
moment,
I
don't
think
we
have
any
evidence
that
any
of
these
compound
these
are
all
actually
acting
at
different
sites.
At
least
that's
the
the
the
ucl
compounds
and
the
atom
wise
compounds
are
not
at
the
same
site.
We've
had
that
discussion
and
they're,
not
at
the
atp
site,
which,
in
theory
what
the
animating
compounds
were
so
at.
B
B
J
N
F
O
F
O
N
K
B
M
M
M
B
O
Well,
I
mean
the
assuming,
let's
say
the
the
seattle
structure:
genomic
center
is
gets
funded,
then
they're
and
all
of
our
approved
projects
just
continue
forward.
There's
no
there's!
No
any
you
don't
have
to
you
know
re-submit
or
anything,
the
the
group.
You
know
the
crystallography
group
that'll
be
that's
taking
over
enough
work.
You
know,
they're
gonna
have
to
hire
a
couple.
People
and
they're,
obviously
not
able
to
hire
until
they
know
that
there
will
be
funds,
and
so
there's
gonna
be,
will
certainly
be
a
lag.
O
O
On
the
chance
that
the
seattle
group,
you
know
if
we
fail
in
our
re
our
bid
and
they
choose
someone
else,
then
the
rules,
I'm.
I
know
that
niaid
the
program
officers
will
want
to
see
this
continue
and
then
they
they
will
most
likely
be
moving.
You
know
maybe
moving
with
a
different
place,
but
obviously
I
can't
speak
for
whoever
takes
over
and
whatever
their
new
process
is
so.
B
Just
think,
just
at
the
mention
of
niaid
we're
just
thinking
about
future
funding
opportunities,
I
mean
I'm
looking
around
the
uk
and
I'm
scratching
my
head
a
little
bit.
I
mean
I'm
just
wondering
whether
whether
they
would
be
open
to
a
conversation
about
helping
to
materially
fund
some
of
the
chemistry
and
biochemistry.
O
G
O
Like
they
don't
get
to,
you
know,
have
they
don't
have
a
pot
of
money
that
they
can
give
to
their
favorite
projects?
They're,
like
oh,
that
sounds
great.
You
should
submit
a
grant
right
and
so
that's
how
what
they
do
and,
of
course
we
know
that
you
know
grants
have
about
a
10
chance
of
getting
funded,
so
not
that
we
shouldn't
submit
grants.
We
should
we
just
it's
not
there's
no
sort
of
like
connection
there.
You
know
I
would.
O
J
J
J
So
that's
the
other
option
and
I
have
a
contact
former
astrazeneca
colleague,
ann
aitken
at
event.
At
niaad-
and
so
that's
that's
something
we
can
we
can.
We
can
talk
about
going
forward
about,
but
I
think
in
the
us
we're
not
we're
not
in
a
position
at
this
point.
As
far
as
I'm
concerned
my
viewpoint
to
do
an
r01,
which
is
the
five
year
program,
because
we
don't
have
strong
enough
data
preliminary
data,
so
the
idea
would
be
to
get
an
r21
generate
that
preliminary
data
that
would
support
an
r01
larger
grant.
J
Yeah
I
mean
that's.
That
would
be,
I
think,
from
the
u.s
side
I
mean
that's
how
I
would
see
the
potential
opportunities
for
funding
yeah
yeah.
But
again
it's
small.
You
know
the
r21
is
very
small.
It's
too,
you
know.
275
000
doesn't
go
very
far
when
you
start
talking
about
the
cost
of
you
know
a
staff,
a
chemist
and
overhead,
and
so
on.
J
G
J
J
I
think
that's
still
the
case
and
actually
carvex
right
now
is
waiting
to
be
refunded
by
the
nih
or
in
iad
I
mean
they.
There
was
a
proposal
put
out
by
niad,
which
basically
was
written
with
carvex
in
mind.
It's
like
carvex,
being
the
only
one
who
could
meet
all
the
rfps,
but
there
they
will
get
refunded.
I'm
sure,
but
that's
still
up
in
the
air,
but
yeah
I
think
carvex
is.
Is
we're
not
really
in
a
good
position
for
carvex?
J
O
Yes,
so
niad
has
consistently
funded
antibiotic
resistance,
drug
development
projects.
They
have
an
rfa
it's
almost
every
year.
I
think-
and
I
saw
one
I
think,
come
out
a
couple
weeks
ago:
they're
very
product
development
oriented
you
have
to
have
a
product
development
plan,
which
you
know
basically
means
you
need
a
pre-clinical
candidate
or
at
least
or
capable
of
getting
to
a
pre-clinical
candidate
within
a
short
period
of
time,
which
is
and
and
that's
true
kind
of
whether
you
talk
to
the
drugs
dndi
or
carbax.
O
K
F
O
B
B
B
You
know
scraping
the
bottom
of
the
barrel
from
local
funding,
just
to
keep
things
going
and
then
finding
how
we
can
push
things
forward
enough
to
go
for
the
medium
and
big
ones
which
we
ought
to
do.
I
mean
we're
getting
some
progress,
we're
getting
some.
You
know
multi
ligase
inhibitors,
which
is
great,
and
that
was
you
know.
The
first
set
of
compounds
screen
two
sets
of
compound
screens
and
we've
got
two
sets
of
dual
targeting
compounds.
So
it's
got
to
be
good.
B
The
reality
of
drug
discovery
very
good,
all
right.
Okay,
I'm
glad
we
got
there
in
the
end
with
the
talk
world
and
andrew
I've
just
have
to
say
the
team
here,
adrian
anita
and
julie,
have
been
working
24
7
over
the
last
couple
of
weeks.
Just
to
get
that
data
out.
It
looks
like
a
few
slides,
but
there's
an
awful
lot
of
data
points
in
there.
So
thank
you
all.