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. Author manuscript; available in PMC: 2014 Oct 15.
Published in final edited form as: Adv Drug Deliv Rev. 2012 Sep 29;65(10):1357–1369. doi: 10.1016/j.addr.2012.09.039

Table 3.

Examples of linkers and their functionalities.

Linker
Function		 Examples
Fusion Protein Linker
 Ref.
Type Sequencea
Increase
Stability/Folding		 scFv flexible (GGGGS)3 [46]
G-CSF-Tf flexible (GGGGS)3 [20]
HBsAg preS1 flexible (GGGGS)3 [85]
Myc- Est2p flexible (Gly)8 [30]
albumin-ANF flexible (Gly)6 [31]
virus coat protein rigid (EAAAK)3 [50]
beta-glucanase-xylanase rigid (EAAAK)n (n=1-3) [52]
Increase
expression		 hGH-Tf and Tf-hGH rigid A(EAAAK)4ALEA(EAAAK)4A [18]
G-CSF-Tf and
Tf-G-CSF		 rigid A(EAAAK)4ALEA(EAAAK)4A [18]
Improve
biological
activity		 G-CSF-Tf flexible (GGGGS)3 [20]
G-CSF-Tf rigid A(EAAAK)4ALEA(EAAAK)4A [20]
hGH-Tf rigid A(EAAAK)4ALEA(EAAAK)4A [40]
HSA-IFN-α2b flexible GGGGS [17]
HSA-IFN-α2b rigid PAPAP [17]
HSA-IFN-α2b rigid AEAAAKEAAAKA [17]
PGA-rTHS flexible (GGGGS)n (n=1, 2, 4) [55]
interferon-γ-gp120 rigid (Ala-Pro)n (10 – 34 aa) [54]
GSF-S-S-Tf cleavable disulfide [39]
IFN-α2b-HSA cleavable disulfide [42]
Enable targeting FIX-albumin cleavable VSQTSKLTR↓AETVFPDVb [59]
LAP-IFN-β cleavable PLG ↓ LWA c [64]
MazE-MazF cleavable RVL↓AEA; EDVVCC↓SMSY;
GGIEGR↓GSc 		[68]
Immunotoxins cleavable TRHRQPR↓GWE;
AGNRVRR↓SVG;
RRRRRRR↓R↓Rd 		[72]
Immunotoxin cleavable GFLG↓e [77]
Alter PK dipeptide LE
G-CSF-Tf and hGH-Tf rigid A(EAAAK)4ALEA(EAAAK)4A [79]
cleavable Disulfide
a

Protease sensitive cleavage sites are indicated with “↓”

b

Factor XIa/FVIIa sensitive cleavage

c

Matrix metalloprotease-1 sensitive cleavage sequences, one example provided here

d

HIV PR (HIV-1 protease); NS3 protease (HCV protease); Factor Xa sensitive cleavage, respectively

e

Furin sensitive cleavage

f

Cathepsin B sensitive cleavage